Sample records for autosomal-recessive pitt-hopkins-like mental

  1. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila

    DEFF Research Database (Denmark)

    Zweier, Christiane; de Jong, Eiko K; Zweier, Markus;


    Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental language disorders, autism spectrum disorders, epilepsy...... protein can reorganize synaptic morphology and induce increased density of active zones, the synaptic domains of neurotransmitter release. Moreover, both Nrx-I and Nrx-IV determine the level of the presynaptic active-zone protein bruchpilot, indicating a possible common molecular mechanism in Nrx......, and schizophrenia. We now identified homozygous and compound-heterozygous deletions and mutations via molecular karyotyping and mutational screening in CNTNAP2 and NRXN1 in four patients with severe mental retardation (MR) and variable features, such as autistic behavior, epilepsy, and breathing anomalies...

  2. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. (United States)

    Zweier, Christiane; de Jong, Eiko K; Zweier, Markus; Orrico, Alfredo; Ousager, Lilian B; Collins, Amanda L; Bijlsma, Emilia K; Oortveld, Merel A W; Ekici, Arif B; Reis, André; Schenck, Annette; Rauch, Anita


    Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental language disorders, autism spectrum disorders, epilepsy, and schizophrenia. We now identified homozygous and compound-heterozygous deletions and mutations via molecular karyotyping and mutational screening in CNTNAP2 and NRXN1 in four patients with severe mental retardation (MR) and variable features, such as autistic behavior, epilepsy, and breathing anomalies, phenotypically overlapping with Pitt-Hopkins syndrome. With a frequency of at least 1% in our cohort of 179 patients, recessive defects in CNTNAP2 appear to significantly contribute to severe MR. Whereas the established synaptic role of NRXN1 suggests that synaptic defects contribute to the associated neuropsychiatric disorders and to severe MR as reported here, evidence for a synaptic role of the CNTNAP2-encoded protein CASPR2 has so far been lacking. Using Drosophila as a model, we now show that, as known for fly Nrx-I, the CASPR2 ortholog Nrx-IV might also localize to synapses. Overexpression of either protein can reorganize synaptic morphology and induce increased density of active zones, the synaptic domains of neurotransmitter release. Moreover, both Nrx-I and Nrx-IV determine the level of the presynaptic active-zone protein bruchpilot, indicating a possible common molecular mechanism in Nrx-I and Nrx-IV mutant conditions. We therefore propose that an analogous shared synaptic mechanism contributes to the similar clinical phenotypes resulting from defects in human NRXN1 and CNTNAP2.

  3. CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila.

    NARCIS (Netherlands)

    Zweier, C.; Jong, E.K. de; Zweier, M.; Orrico, A.; Ousager, L.B.; Collins, A.L.; Bijlsma, E.K.; Oortveld, M.A.W.; Ekici, A.B.; Reis, A.; Schenck, A.; Rauch, A.


    Heterozygous copy-number variants and SNPs of CNTNAP2 and NRXN1, two distantly related members of the neurexin superfamily, have been repeatedly associated with a wide spectrum of neuropsychiatric disorders, such as developmental language disorders, autism spectrum disorders, epilepsy, and schizophr

  4. Autosomal recessive disorder with retardation of growth, mental deficiency, ptosis, pectus excavatum and camptodactyly

    Energy Technology Data Exchange (ETDEWEB)

    Khaldi, F.; Bennaceur, B.; Hammou, A.; Hamza, M.; Gharbi, H.A.


    Two strikingly similar brothers issued from consanguineous parents in the second degree present the following patterns of anomalies: Retardation of growth, mental deficiency, ocular abnormalities, pectus excavatum and camptodactyly. The ocular abnormalities include ptosis, microphthalmia and hypertelorism. No endocrine or metabolic aberrations are found. The authors conclude that the disorder has probably an autosomal recessive mode of transmission.

  5. Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel

    DEFF Research Database (Denmark)

    Rehman, Shoaib ur; Baig, Shahid Mahmood; Eiberg, Hans;


    Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive men...

  6. Autosomal recessive mental retardation syndrome with anterior maxillary protrusion and strabismus: MRAMS syndrome. (United States)

    Basel-Vanagaite, Lina; Rainshtein, Limor; Inbar, Dov; Gothelf, Doron; Hennekam, Raoul; Straussberg, Rachel


    We report on a family in whom the combination of mental retardation (MR), anterior maxillary protrusion, and strabismus segregates. The healthy, consanguineous parents (first cousins) of Israeli-Arab descent had 11 children, 7 of whom (5 girls) were affected. They all had severe MR. Six of the seven had anterior maxillary protrusion with vertical maxillary excess, open bite, and prominent crowded teeth. None of the sibs with normal intelligence had jaw or dental anomalies. The child with MR but without a jaw anomaly was somewhat less severely retarded, had seizures and severe psychosis, which may point to his having a separate disorder. Biochemical and neurological studies, including brain MRI and standard cytogenetic studies, yielded normal results; fragile X was excluded, no subtelomeric rearrangements were detectable, and X-inactivation studies in the mother showed random inactivation. We have been unable to find a similar disorder in the literature, and suggest that this is a hitherto unreported autosomal recessive disorder, which we propose to name MRAMS (mental retardation, anterior maxillary protrusion, and strabismus).

  7. Computational analysis of TRAPPC9: candidate gene for autosomal recessive non-syndromic mental retardation. (United States)

    Khattak, Naureen Aslam; Mir, Asif


    Mental retardation (MR)/ intellectual disability (ID) is a neuro-developmental disorder characterized by a low intellectual quotient (IQ) and deficits in adaptive behavior related to everyday life tasks such as delayed language acquisition, social skills or self-help skills with onset before age 18. To date, a few genes (PRSS12, CRBN, CC2D1A, GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23, MAN1B1, NSUN1) for autosomal-recessive forms of non syndromic MR (NS-ARMR) have been identified and established in various families with ID. The recently reported candidate gene TRAPPC9 was selected for computational analysis to explore its potentially important role in pathology as it is the only gene for ID reported in more than five different familial cases worldwide. YASARA (12.4.1) was utilized to generate three dimensional structures of the candidate gene TRAPPC9. Hybrid structure prediction was employed. Crystal Structure of a Conserved Metalloprotein From Bacillus Cereus (3D19-C) was selected as best suitable template using position-specific iteration-BLAST. Template (3D19-C) parameters were based on E-value, Z-score and resolution and quality score of 0.32, -1.152, 2.30°A and 0.684 respectively. Model reliability showed 93.1% residues placed in the most favored region with 96.684 quality factor, and overall 0.20 G-factor (dihedrals 0.06 and covalent 0.39 respectively). Protein-Protein docking analysis demonstrated that TRAPPC9 showed strong interactions of the amino acid residues S(253), S(251), Y(256), G(243), D(131) with R(105), Q(425), W(226), N(255), S(233), its functional partner 1KBKB. Protein-protein interacting residues could facilitate the exploration of structural and functional outcomes of wild type and mutated TRAPCC9 protein. Actively involved residues can be used to elucidate the binding properties of the protein, and to develop drug therapy for NS-ARMR patients.

  8. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance? (United States)

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C


    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  9. A new autosomal recessive syndrome characterized by ocular hypertelorism, distinctive face, mental retardation, brachydactyly, and genital abnormalities. (United States)

    Spiegel, Ronen; Horovitz, Yoseph; Peters, Hartmut; Erdogan, Fikret; Chervinsky, Ilana; Shalev, Stavit A


    We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity (combination of upper pectus carinatum with lower pectus excavatum), and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widow's peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition.

  10. Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3-q25.1. (United States)

    Dursun, Umut; Koroglu, Cigdem; Kocasoy Orhan, Elif; Ugur, Sibel Aylin; Tolun, Aslihan


    Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity in the lower limbs. They are clinically heterogeneous, and pure forms as well as complicated forms with other accompanying clinical findings are known. HSPs are also genetically heterogeneous. We performed clinical and genetic studies in a consanguineous family with five affected members. A genome scan using 405 microsatellite markers for eight members of the family identified candidate gene loci, and subsequent fine mapping in 16 members identified the gene locus responsible for the HSP. The clinical manifestations were very early onset spastic paraplegia (SPG) accompanied by mental retardation and ocular signs. The gene locus was identified as the interval 102.05-106.64 Mbp on chromosome 10. Gene MRPL43 was analyzed in the patients. No mutation but high levels of mRNA were detected. We have mapped a novel autosomal recessive complicated form of HSP (SPG45) to a 4.6-Mbp region at 10q24.3-q25.1 with multipoint logarithm of odds scores >4.5.

  11. [Autosomal recessive polycystic kidney]. (United States)

    Todorov, V; Penkova, S; Lalev, I


    A case of a 22 years old woman with autosomal-recessive form of kidney polycystosis is presented. The diagnosis was made in early childhood. A combination of renal anomaly and hepatic fibrosis with manifestations of portal hypertension was present. No deviations from the other internal organs were found. At the age of 12 she entered into the stage of chronic renal failure. The last five years she is on dialysis treatment. She had survived several acute bleedings from esophageal varices. The authors are of the opinion that the case is of interest since patients with autosomal-recessive renal polycystosis very rarely reach majority.

  12. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3. (United States)

    Uyguner, O; Kayserili, H; Li, Y; Karaman, B; Nürnberg, G; Hennies, Hc; Becker, C; Nürnberg, P; Başaran, S; Apak, M Y; Wollnik, B


    Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.

  13. An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4. (United States)

    Kahrizi, Kimia; Najmabadi, Hossein; Kariminejad, Roxana; Jamali, Payman; Malekpour, Mahdi; Garshasbi, Masoud; Ropers, Hans Hilger; Kuss, Andreas Walter; Tzschach, Andreas


    We report on three siblings with a novel mental retardation (MR) syndrome who were born to distantly related Iranian parents. The clinical problems comprised severe MR, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bilateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4 flanked by SNPs rs728293 (4p12) and rs1105434 (4q12). This interval contains more than 40 genes, none of which has been implicated in MR so far. The identification of the causative gene defect for this syndrome will provide new insights into the development of the brain and the eye.

  14. Autosomal recessive epidermolytic palmoplantar keratoderma. (United States)

    Alsaleh, Q A; Teebi, A S


    Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders. Epidermolytic PPK is a well delineated autosomal dominant entity, but no recessive form is known. Here we report two sons of phenotypically normal, consanguineous, Arab parents with features suggestive of PPK. They presented with patchy eczematous skin lesions followed by PPK and raised serum levels of IgE. Skin biopsy from the keratotic lesions showed the features of epidermolytic hyperkeratosis. Autosomal recessive inheritance is suggested and the differential diagnosis is discussed.

  15. A new autosomal recessive non-progressive congenital cerebellar ataxia associated with mental retardation, optic atrophy, and skin abnormalities (CAMOS) maps to chromosome 15q24-q26 in a large consanguineous Lebanese Druze Family. (United States)

    Delague, Valérie; Bareil, Corinne; Bouvagnet, Patrice; Salem, Nabiha; Chouery, Eliane; Loiselet, Jacques; Mégarbané, André; Claustres, Mireille


    Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26.

  16. Autosomal recessive hereditary auditory neuropathy

    Institute of Scientific and Technical Information of China (English)

    王秋菊; 顾瑞; 曹菊阳


    Objectives: Auditory neuropathy (AN) is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses (ABRs) and normal cochlear outer hair cell function as measured by otoacoustic emissions (OAEs). Many risk factors are thought to be involved in its etiology and pathophysiology. Three Chinese pedigrees with familial AN are presented herein to demonstrate involvement of genetic factors in AN etiology. Methods: Probands of the above - mentioned pedigrees, who had been diagnosed with AN, were evaluated and followed up in the Department of Otolaryngology Head and Neck Surgery, China PLA General Hospital. Their family members were studied and the pedigree diagrams were established. History of illness, physical examination,pure tone audiometry, acoustic reflex, ABRs and transient evoked and distortion- product otoacoustic emissions (TEOAEs and DPOAEs) were obtained from members of these families. DPOAE changes under the influence of contralateral sound stimuli were observed by presenting a set of continuous white noise to the non - recording ear to exam the function of auditory efferent system. Some subjects received vestibular caloric test, computed tomography (CT)scan of the temporal bone and electrocardiography (ECG) to exclude other possible neuropathy disorders. Results: In most affected subjects, hearing loss of various degrees and speech discrimination difficulties started at 10 to16 years of age. Their audiological evaluation showed absence of acoustic reflex and ABRs. As expected in AN, these subjects exhibited near normal cochlear outer hair cell function as shown in TEOAE & DPOAE recordings. Pure- tone audiometry revealed hearing loss ranging from mild to severe in these patients. Autosomal recessive inheritance patterns were observed in the three families. In Pedigree Ⅰ and Ⅱ, two affected brothers were found respectively, while in pedigree Ⅲ, 2 sisters were affected. All the patients were otherwise normal without

  17. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1 (United States)

    ... Genetics Home Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by ...

  18. A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum. (United States)

    Boukhris, Amir; Feki, Imed; Elleuch, Nizar; Miladi, Mohamed Imed; Boland-Augé, Anne; Truchetto, Jérémy; Mundwiller, Emeline; Jezequel, Nadia; Zelenika, Diana; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni


    Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.


    NARCIS (Netherlands)



    The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, severely impaired mental and motor development, and extrapyramidal dyskinesia is a distinct system degeneration, previously designated pontocerebellar hypoplasia type 2 (PCH-2). To further characterize its clinical and neu

  20. Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report

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    Rafael Fabiano Machado Rosa

    Full Text Available CONTEXT: The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis.CASE REPORT: Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives. The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the child's head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy.CONCLUSIONS: The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.

  1. Autosomal recessive cerebellar ataxias : the current state of affairs

    NARCIS (Netherlands)

    Vermeer, S.; van de Warrenburg, B. P. C.; Willemsen, M. A. A. P.; Cluitmans, M.; Scheffer, H.; Kremer, B. P.; Knoers, N. V. A. M.


    Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, an

  2. A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: Report of a case and review of literature

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    Phadke Shubha


    Full Text Available Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed.

  3. Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

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    Dayananda Kumar Rajanna


    Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease.

  4. Genetics Home Reference: autosomal recessive spastic ataxia of Charlevoix-Saguenay (United States)

    ... Genetics Home Health Conditions ARSACS autosomal recessive spastic ataxia of Charlevoix-Saguenay Enable Javascript to view the ... Open All Close All Description Autosomal recessive spastic ataxia of Charlevoix-Saguenay , more commonly known as ARSACS , ...

  5. Gonadal mosaicism as a rare cause of autosomal recessive inheritance. (United States)

    Anazi, S; Al-Sabban, E; Alkuraya, F S


    Autosomal recessive diseases are typically caused by the biparental inheritance of familial mutant alleles. Unusual mechanisms by which the recessiveness of a mutant allele is unmasked include uniparental isodisomy and the occurrence of a de novo chromosomal rearrangement that disrupts the other allele. Gonadal mosaicism is a condition in which a postfertilization mutation is confined to the gamete precursors and is not detected in somatic tissues. Gonadal mosaicism is known to give the impression of autosomal recessive inheritance when recurrence of an autosomal-dominant condition among offspring of phenotypically normal parents is observed. Here, we report an extremely rare event in which maternal gonadal mosaicism for a recessive mutation in COL4A4 caused the recurrence of Alport syndrome within a consanguineous family. Such rare occurrence should be taken into account when analyzing pedigrees both for clinical and research purposes.

  6. Mutations of the tyrosinase gene produce autosomal recessive ocular albinism

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    King, R.A.; Summers, C.G.; Oetting, W.S. [Univ. of Minnesota, Minneapolis, MN (United States)] [and others


    Albinism has historically been divided into ocular (OA) and oculocutaneous (OCA) types based on the presence or absence of clinically apparent skin and hair involvement in an individual with the ocular features of albinism. The major genes for OCA include the tyrosinase gene in OCA1 and the P gene in OCA2. X-linked and autosomal recessive OA have been described and the responsible genes have not been identified. We now present six Caucasian individuals who have the phenotype of autosomal recessive OA but who have OCA1 as shown by the presence of mutations of the tyrosinase. They had white or very light hair and white skin at birth, and cutaneous pigment developed in the first decade of life. At ages ranging from 1.5-23 years, hair color was dark blond to light brown. The skin had generalized pigment and well developed tan was present on the exposed arm and face skin of four. Iris pigment was present and iris translucency varied. Molecular analysis of the tyrosinase gene, using PCR amplification and direct di-deoxy sequencing showed the following mutations: E398Z/E398Q, P406S/g346a, R402E/T373K, ?/D383N, and H211N/T373K. The homozygous individual was not from a known consanguineous mating. T373K is the most common tyrosinase gene mutation in our laboratory. Three of these mutations are associated with a total loss of tyrosinase activity (g346a splice-site, T373K, and D383N), while four are associated with residual enzyme activity (H211N, R402E, E398Q, and P406S). These studies show that mutations of the tyrosinase gene can produce the phenotype of autosomal recessive OA in an individual who has normal amounts of cutaneous pigment and the ability to tan after birth. This extends the phenotypic range of OCA1 to normal cutaneous pigment after early childhood, and suggest that mutations of the tyrosinase gene account for a significant number of individuals with autosomal recessive OA.

  7. A novel deletion mutation in ASPM gene in an Iranian family with autosomal recessive primary microcephaly

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    , Springell K, Corry P, Abramowicz MJ, et al. Protein-Truncating Mutations in< i> ASPM Cause Variable Reduction in Brain Size. The American Journal of Human Genetics 2003;73(5:1170-7.26. Pichon B, Vankerckhove S, Bourrouillou G, Duprez L, Abramowicz MJ. A translocation breakpoint disrupts the ASPM gene in a patient with primary microcephaly. European journal of Human Genetics 2004;12(5:419-21.27. Garshasbi.M, Motazacker M, Kahrizi K, Behjati F, Abedini S, Nieh S, et al. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly. Hum Genet 2006 Feb;118(6:708-15.28. Jackson A, McHale D, Campbell D, Jafri H, Rashid Y, Mannan J, et al. Primary autosomal recessive microcephaly (MCPH1 maps to chromosome 8p22-pter. Am J Hum Genet 1998 Aug;63(2:541-6.29. Moynihan L, Jackson A, Roberts E, Karbani G, Lewis I, Corry P, et al. A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34. Am J Hum Genet 2000 Feb;66(2:724-7.30. Bond J, Roberts E, Springell K, Lizarraga S, Scott S, Higgins J, et al. A centrosomalmechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet.2005 Apr;37(4:353-5. Nat Genet 2005 Apr;37(4:353-5.31. Jamieson C, Govaerts C, Abramowicz M, J. Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. Am J Hum Genet. 1999;65:1465-9.

  8. The Autosomal Recessive Inheritance of Hereditary Gingival Fibromatosis

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    Poulami Majumder


    Full Text Available Hereditary gingival fibromatosis (HGF is a rare condition which is marked by enlargement of gingival tissue that covers teeth to various extents leading to aesthetic disfigurement. This study presents a case of a 28-year-old female patient and 18-year-old male who belong to the same family suffering from HGF with chief complaint of overgrowing swelling gingiva. The presence of enlarged gingiva with the same eruption was found in their other family members with no concomitant drug or medical history, and the occurrence of HGF has been found in one generation of this family which may indicate the autosomal recessive inheritance pattern of HGF. Hereditary gingival fibromatosis is an idiopathic condition as its etiology is unknown and it was found to recur in some cases even after surgical treatment. Both patients underwent thorough oral prophylaxis and later surgical therapy to correct the deformity.

  9. Molecular and Cellular Basis of Autosomal Recessive Primary Microcephaly

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    Marine Barbelanne


    Full Text Available Autosomal recessive primary microcephaly (MCPH is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development.

  10. Connexin 26 and autosomal recessive non-syndromic hearing loss

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    Mukherjee Monisha


    Full Text Available Prelingual deafness occurs with a frequency of 1 in 1000 live births and is divided into syndromic and non-syndromic forms contributing 40 and 60% respectively. Autosomal recessive non-syndromic hearing loss (ARNSHL is responsible for 80% cases of childhood deafness. Nearly all genes localized for ARNSHL cause prelingual, severe to profound, sensorineural hearing impairment. ARNSHL is genetically heterogeneous and at least 39 loci have been identified. The most significant finding to date has been the discovery of mutations in GJB2 gene at the DFNB1 locus on chromosome 13q12 as the major cause of profound prelingual deafness. This was first reported in a Tunisian family in 1994 and thereafter in many different countries. GJB2 gene encodes the gap-junction protein, connexin 26 (Cx26, mutations in which have become the first genetic marker of inherited hearing loss. Allele-specific polymerase chain reaction (AS-PCR, single stranded conformation polymorphism (SSCP and sequencing methods have been developed for the detection of mutations in Cx26 gene. In India as well, the Cx26 mutations are being screened in families with hearing impaired children using these molecular methods. Therefore, in order to create awareness among the clinicians and the affected families; we have attempted to review the Cx26 gene mutations responsible for autosomal recessive type of non-syndromic hearing loss. The efficacy and utility of Cx26 gene analysis might open the path to proper counseling of families for carrier detection and prenatal diagnosis. It may even facilitate the development of strategies in future for the treatment of this common genetic disorder.

  11. FOXE3 plays a significant role in autosomal recessive microphthalmia. (United States)

    Reis, Linda M; Tyler, Rebecca C; Schneider, Adele; Bardakjian, Tanya; Stoler, Joan M; Melancon, Serge B; Semina, Elena V


    FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop normally. In humans, autosomal dominant and recessive mutations in FOXE3 have been associated with variable phenotypes including anterior segment anomalies, cataract, and microphthalmia. We undertook sequencing of FOXE3 in 116 probands with a spectrum of ocular defects ranging from anterior segment dysgenesis and cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found in four of 26 probands affected with bilateral microphthalmia (15% of all bilateral microphthalmia and 100% of consanguineous families with this phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or corneal defects; no other associated systemic anomalies were observed in FOXE3-positive families. The previously reported c.720C > A (p.C240X) nonsense mutation was identified in two additional families in our sample and therefore appears to be recurrent, now reported in three independent microphthalmia families of varied ethnic backgrounds. Several missense variants were identified at varying frequencies in patient and control groups with some apparently being race-specific, which underscores the importance of utilizing race/ethnicity-matched control populations in evaluating the relevance of genetic screening results. In conclusion, FOXE3 mutations represent an important cause of nonsyndromic autosomal recessive bilateral microphthalmia.

  12. An exome sequencing strategy to diagnose lethal autosomal recessive disorders. (United States)

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana


    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0-4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.

  13. Autosomal recessive agammaglobulinemia: a novel non-sense mutation in CD79a. (United States)

    Khalili, Abbas; Plebani, Alessandro; Vitali, Massimiliano; Abolhassani, Hassan; Lougaris, Vassilios; Mirminachi, Babak; Rezaei, Nima; Aghamohammadi, Asghar


    This study describes the fifth case worldwide of autosomal recessive agammaglobulinemia due to a novel non-sense mutation in CD79a gene with a severe unusual onset due to an invasive central nervous system infection.

  14. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.

    NARCIS (Netherlands)

    Kohl, S.; Varsanyi, B.; Antunes, G.A.; Baumann, B.; Hoyng, C.B.; Jagle, H.; Rosenberg, T.; Kellner, U.; Lorenz, B.; Salati, R.; Jurklies, B.; Farkas, A.; Andreasson, S.; Weleber, R.G.; Jacobson, S.G.; Rudolph, G.; Castellan, C.; Dollfus, H.; Legius, E.; Anastasi, M.; Bitoun, P.; Lev, D.; Sieving, P.A.; Munier, F.L.; Zrenner, E.; Sharpe, L.T.; Cremers, F.P.M.; Wissinger, B.


    Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum

  15. Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families

    NARCIS (Netherlands)

    Gasparini, P; Estivill, [No Value; Volpini, [No Value; Totaro, A; CastellviBel, S; Govea, N; Mila, M; DellaMonica, M; Ventruto, [No Value; DeBenedetto, M; Stanziale, P; Zelante, L; Mansfield, ES; Sandkuijl, L; Surrey, S; Fortina, P


    Recent studies show a susceptibility locus (DFNB1) responsible for non-syndromic neurosensory autosomal-recessive deafness (NSRD) mapping to the pericentromeric region of chromosome 13q, In order to better understand the frequency with which DFNB1 is the gene for deafness in our patient population a

  16. Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

    NARCIS (Netherlands)

    C. Sevin; S. Ferdinandusse; H.R. Waterham; R.J. Wanders; P. Aubourg


    ABSTRACT: OBJECTIVE: To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA). Case report: Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of bl

  17. Progeria (Hutchison-Gilford syndrome) in siblings: in an autosomal recessive pattern of inheritance. (United States)

    Raghu, T Y; Venkatesulu, G A; Kantharaj, G R; Suresh, T; Veeresh, V; Hanumanthappa, Y


    Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclerodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  18. A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia.

    NARCIS (Netherlands)

    Kohl, S.; Coppieters, F.; Meire, F.; Schaich, S.; Roosing, S.; Brennenstuhl, C.; Bolz, S.; Genderen, M.M. van; Riemslag, F.C.; Lukowski, R.; Hollander, A.I. den; Cremers, F.P.M.; Baere, E. de; Hoyng, C.B.; Wissinger, B.


    Achromatopsia (ACHM) is an autosomal-recessive retinal dystrophy characterized by color blindness, photophobia, nystagmus, and severely reduced visual acuity. Its prevalence has been estimated to about 1 in 30,000 individuals. Four genes, GNAT2, PDE6C, CNGA3, and CNGB3, have been implicated in ACHM,

  19. Progeria (Hutchison - Gilford syndrome in siblings: In an autosomal recessive pattern of inheritance

    Directory of Open Access Journals (Sweden)

    Raghu Tanjore


    Full Text Available Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclcrodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  20. Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease.

    NARCIS (Netherlands)

    Zingg-Schenk, A.; Caduff, J.; Azzarello-Burri, S.; Bergmann, C.; Drenth, J.P.H.; Neuhaus, T.J.


    BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was rep

  1. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio


    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  2. Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, Yin Y.; Banerjee, P.; Knowles, J.A. [Columbia Univ., New York, NY (United States)] [and others


    The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS. 26 refs., 2 figs., 1 tab.

  3. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat

    Energy Technology Data Exchange (ETDEWEB)

    Casimir, C.M.; Bu-Ghanim, H.N.; Rowe, P.; Segal, A.W. (University College London (England)); Rodaway, A.R.F.; Bentley, D.L. (Imperial Cancer Research Fund Lab., London (England))


    Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b{sub 245}). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, {gt}90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. The authors demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron - exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene.

  4. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case]. (United States)

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A


    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  5. New form of autosomal-recessive axonal hereditary sensory motor neuropathy. (United States)

    Eckhardt, S M; Hicks, E M; Herron, B; Morrison, P J; Aicardi, J


    Two siblings, a male and a female, had severe axonal neuropathy and sideroblastic anemia. Despite a distinct clinical picture with areflexia, ataxia, hypotonia, optic atrophy, and progressive sensory neural hearing loss, no definite diagnosis could be reached and the older sibling died at 6 years of age of respiratory failure. It is proposed that the two affected siblings have a new form of autosomal-recessive axonal hereditary sensory motor neuropathy.

  6. More Than Ataxia: Hyperkinetic Movement Disorders in Childhood Autosomal Recessive Ataxia Syndromes



    Background The autosomal recessive ataxias are a heterogeneous group of disorders that are characterized by complex neurological features in addition to progressive ataxia. Hyperkinetic movement disorders occur in a significant proportion of patients, and may sometimes be the presenting motor symptom. Presentations with involuntary movements rather than ataxia are diagnostically challenging, and are likely under-recognized. Methods A PubMed literature search was performed in October 2015 util...

  7. Macroepiphyseal dysplasia with symptomatic osteoporosis, wrinkled skin, and aged appearance: A presumed autosomal recessive condition

    Energy Technology Data Exchange (ETDEWEB)

    McAlister, W.H.; Coe, J.D.; Whyte, M.P.


    We report our detailed investigation of a 7-1/2-year-old girl with short stature, aged appearance, decreased subcutaneous fat and muscle mass, dry coarse hair, foot deformities, macroepiphyses with prominent but lax joints, and osteoporosis with recurrent fractures who is the offspring of first cousins. This constellation of abnormalities differs from previously reported cases where macroepiphyses were a prominent finding. Our patient appears, therefore, to have a new, autosomal recessively inherited, syndrome.

  8. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy. (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H


    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  9. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Directory of Open Access Journals (Sweden)

    K J Kelly

    Full Text Available Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  10. Coincidence the Autosomal Recessive Polycystic Kidney Disease With Placenta Membranacea (A Probably Genetic Relation with PKHD1 Gene

    Directory of Open Access Journals (Sweden)

    Ehsan Hosseini


    Full Text Available Placenta membranacea is one of the most barley anomalies happens in pregnancy defined by chorionic villi (partially or completely covered the fetus membrane. Autosomal recessive polycystic kidney disease in fetus is also a rare case with an incidence of 1: 20,000 live births resulting in a 30% death rate in neonates. In this case for the first time, we reported a placenta membranacea and autosomal recessive polycystic kidney disease occurred with together. A 25-year-old woman was admitted at 16 weeks of gestation for inducing abortion with autosomal recessive polycystic kidney disease in fetus diagnosed in routine sonography fellowship. Post-delivery examination revealed a placenta totally enveloped the fetus, oligohydramnious and bilateral enlarged polycystic kidneys of fetus. Histological study indicated umbilicus has only one artery and one vein as well as autosomal recessive polycystic kidney disease and directly attachment of chorionic villi to fetal membrane eventually diagnosed as complete placenta membranacea. The etiology of placenta membranacea is not completely clarified. As autosomal recessive polycystic kidney disease is a result of mutation in PKHD1 gene, so our finding may be initiates a new investigation about genetic relation between placenta membranacea and autosomal recessive polycystic kidney disease.

  11. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. (United States)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas


    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans.

  12. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant). (United States)

    Bichet, Daniel G; Bockenhauer, Detlef


    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.

  13. Founder mutation in dystonin-e underlying autosomal recessive epidermolysis bullosa simplex in Kuwait. (United States)

    Takeichi, T; Nanda, A; Liu, L; Aristodemou, S; McMillan, J R; Sugiura, K; Akiyama, M; Al-Ajmi, H; Simpson, M A; McGrath, J A


    Only two homozygous nonsense mutations in the epidermal isoform of the dystonin gene, DST-e, have been reported previously in autosomal recessive epidermolysis bullosa simplex (EBS); the affected pedigrees were Kuwaiti and Iranian. This subtype of EBS is therefore considered to be a rare clinicopathological entity. In this study, we identified four seemingly unrelated Kuwaiti families in which a total of seven individuals had predominantly acral trauma-induced blistering since infancy. All affected individuals were homozygous for the mutation p.Gln1124* in DST-e, the same mutation that was identified in the originally reported family from Kuwait. Haplotype analysis in the five pedigrees (including the previous case) revealed a shared block of ~60 kb of genomic DNA across the site of the mutation, consistent with a founder effect. Most heterozygotes had no clinical abnormalities although one subject had mild transient skin fragility during childhood, an observation noted in the previously reported Iranian pedigree, suggesting that the condition may also be semidominant in some pedigrees rather than purely autosomal recessive. Our study reveals propagation of a mutant ancestral allele in DST-e throughout Kuwait, indicating that this subtype of EBS may be more common in Kuwait, and perhaps other Middle Eastern countries, than is currently appreciated.

  14. Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.

    Directory of Open Access Journals (Sweden)

    Dirk J Lefeber


    Full Text Available Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5-13 years with a predominant presentation of dilated cardiomyopathy (DCM. Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG. Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations.

  15. Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family. (United States)

    Chograni, M; Alkuraya, F S; Ourteni, I; Maazoul, F; Lariani, I; Chaabouni, H B


    The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

  16. Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans.

    Directory of Open Access Journals (Sweden)

    Franz P W Radner


    Full Text Available Autosomal recessive congenital ichthyosis (ARCI is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3 and abolishes a sequence for a long non-coding RNA (FLJ42289. Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3 and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis.

  17. Autosomal recessive transmission of MYBPC3 mutation results in malignant phenotype of hypertrophic cardiomyopathy.

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    Yilu Wang

    Full Text Available BACKGROUND: Hypertrophic cardiomyopathy (HCM due to mutations in genes encoding sarcomere proteins is most commonly inherited as an autosomal dominant trait. Since nearly 50% of HCM cases occur in the absence of a family history, a recessive inheritance pattern may be involved. METHODS: A pedigree was identified with suspected autosomal recessive transmission of HCM. Twenty-six HCM-related genes were comprehensively screened for mutations in the proband with targeted second generation sequencing, and the identified mutation was confirmed with bi-directional Sanger sequencing in all family members and 376 healthy controls. RESULTS: A novel missense mutation (c.1469G>T, p.Gly490Val in exon 17 of MYBPC3 was identified. Two siblings with HCM were homozygous for this mutation, whereas other family members were either heterozygous or wild type. Clinical evaluation showed that both homozygotes manifested a typical HCM presentation, but none of others, including 5 adult heterozygous mutation carriers up to 71 years of age, had any clinical evidence of HCM. CONCLUSIONS: Our data identified a MYBPC3 mutation in HCM, which appeared autosomal recessively inherited in this family. The absence of a family history of clinical HCM may be due to not only a de novo mutation, but also recessive mutations that failed to produce a clinical phenotype in heterozygous family members. Therefore, consideration of recessive mutations leading to HCM is essential for risk stratification and genetic counseling.

  18. Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations (United States)

    Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert


    Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

  19. A Linkage Study in 8 Pakistani Families Segregating as Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    M. Hassanullah


    Full Text Available The current study was designed to find the most frequent MCPH phenotype in inbred Pakistani families. Primary microcephaly is marked by small brain size and is usually inherited as recessive trait. In the present study, we performed linkage analysis on 8 Pakistani families with autosomal recessive primary microcephaly (MCPH and linked 6 of them to known MCPH genes/loci like MCPH1 (Microcephalin, MCPH3 (CDK5RAP2 and MCPH5 (ASPM. Majority of the families showed linkage with MCPH5, the most common MCPH locus in Pakistan. The linked families were then subjected to mutational analysis, revealing a previously known G to A transition at nucleotide position 3978 in exon 17 of ASPM gene in three of the families. To decrease its incidence, it is indispensible to train the people of the possible devastating outcome of cousin marriages and to find the carriers through carrier screening programs.

  20. Autosomal recessive chronic granulomatous disease presenting with cutaneous dermatoses and ocular infection. (United States)

    Low, L C M; Manson, A L; Hardman, C; Carton, J; Seneviratne, S L; Ninis, N


    Dermatoses such as eczematous dermatitis and cutaneous infection are recognized presentations of primary immunodeficiency (PID). However, atopic dermatitis affects approximately 10% of infants, and cutaneous infections are not uncommon in children, therefore the challenge for the dermatologist is to distinguish the few patients that have PID from the many that do not. We report on a 6-year-old girl who was ultimately diagnosed with autosomal recessive chronic granulomatous disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp plaques recalcitrant to treatment, and recurrent infections over a 3-year period, and describe some aspects of her diagnosis and management. This report highlights the importance of considering rare disorders such as AR-CGD in the differential diagnosis of recurrent or recalcitrant dermatological infections in children.

  1. Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Ek, Jakob; Sand, Annie;


    PURPOSE: The study was initiated to investigate the mutation spectrum of four OCA genes and to calculate the birth prevalence in patients with autosomal recessive albinism. METHODS: Mutation analysis using dHPLC or direct DNA sequencing of TYR, OCA2, TYRP1, and MATP was performed in 62 patients....... Two mutations in one OCA gene explained oculocutaneous albinism (OCA) in 44% of the patients. Mutations in TYR were found in 26% of patients, while OCA2 and MATP caused OCA in 15% and 3%, respectively. No mutations were found in TYRP1. Of the remaining 56% of patients, 29% were heterozygous...... recessive ocular albinism (AROA) based on clinical findings was 55 to 45. CONCLUSIONS: TYR is the major OCA gene in Denmark, but several patients do not have mutations in the investigated genes. A relatively large fraction of patients were observed with AROA, and of those 52% had no mutations compared...

  2. Root anomalies and dentin dysplasia in autosomal recessive hyperphosphatemic familial tumoral calcinosis (HFTC) (United States)

    Vieira, Alexandre R.; Lee, Moses; Vairo, Filippo; Leite, Julio Cesar Loguercio; Munerato, Maria Cristina; Visioli, Fernanda; D’Ávila, Stéphanie Rodrigues; Wang, Shih-Kai; Choi, Murim; Simmer, James P.; Hu, Jan C-C.


    Hyperphosphatemic familial tumoral calcinosis (HFTC, OMIM #211900) is an autosomal recessive metabolic disorder characterized by hyperphosphatemia, tooth root defects, and the progressive deposition of calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone.1 In this HFTC case report, we document the dental phenotype associated with a homozygous missense mutation (g.29077 C>T; c.484 C>T; p.Arg162*) in GALNT3 (OMIM 6017563), a gene encoding UDP-GalNAc transferase 3 that catalyzes the first step of O-linked oligosaccharide biosynthesis in the Golgi. The medical and dental pathology is believed to be caused primarily by high serum phosphate levels (hyperphosphatemia), which, in turn, is caused by failure of GALNT3 to glycosylate the phosphate regulator protein FGF23, impairing its ability inhibit reabsorption of filtered phosphate in the kidneys. PMID:26337219

  3. [Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease]. (United States)


    Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis- medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

  4. A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family. (United States)

    Singh, Nivedita; Kumble Bhat, Vishwanath; Tiwari, Ankana; Kodaganur, Srinivas G; Tontanahal, Sagar J; Sarda, Astha; Malini, K V; Kumar, Arun


    Anencephaly is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to anencephaly. Anencephaly shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of anencephaly has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C>A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive anencephaly (APH) in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silco analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared to cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to anencephaly.

  5. ABCA4 gene analysis in patients with autosomal recessive cone and cone rod dystrophies. (United States)

    Kitiratschky, Veronique B D; Grau, Tanja; Bernd, Antje; Zrenner, Eberhart; Jägle, Herbert; Renner, Agnes B; Kellner, Ulrich; Rudolph, Günther; Jacobson, Samuel G; Cideciyan, Artur V; Schaich, Simone; Kohl, Susanne; Wissinger, Bernd


    The ATP-binding cassette (ABC) transporters constitute a family of large membrane proteins, which transport a variety of substrates across membranes. The ABCA4 protein is expressed in photoreceptors and possibly functions as a transporter for N-retinylidene-phosphatidylethanolamine (N-retinylidene-PE), the Schiff base adduct of all-trans-retinal with PE. Mutations in the ABCA4 gene have been initially associated with autosomal recessive Stargardt disease. Subsequent studies have shown that mutations in ABCA4 can also cause a variety of other retinal dystrophies including cone rod dystrophy and retinitis pigmentosa. To determine the prevalence and mutation spectrum of ABCA4 gene mutations in non-Stargardt phenotypes, we have screened 64 unrelated patients with autosomal recessive cone (arCD) and cone rod dystrophy (arCRD) applying the Asper Ophthalmics ABCR400 microarray followed by DNA sequencing of all coding exons of the ABCA4 gene in subjects with single heterozygous mutations. Disease-associated ABCA4 alleles were identified in 20 of 64 patients with arCD or arCRD. In four of 64 patients (6%) only one mutant ABCA4 allele was detected and in 16 patients (25%), mutations on both ABCA4 alleles were identified. Based on these data we estimate a prevalence of 31% for ABCA4 mutations in arCD and arCRD, supporting the concept that the ABCA4 gene is a major locus for various types of degenerative retinal diseases with abnormalities in cone or both cone and rod function.

  6. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

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    Sundaramurthy Srilekha

    Full Text Available Leber congenital amaurosis (LCA and retinitis pigmentosa (RP are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60% mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

  7. Autosomal recessive PGM3 mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment (United States)

    Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie; Lyons, Jonathan J.; Datta, Shrimati; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; Biancalana, Matthew; Wolfe, Lynne A.; DiMaggio, Thomas; Matthews, Helen F.; Kranick, Sarah M.; Stone, Kelly D.; Holland, Steven M.; Reich, Daniel S.; Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua; Freeman, Alexandra F.; Freeze, Hudson H.; Su, Helen C.; Milner, Joshua D.


    Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective To define a genetic syndrome of severe atopy, elevated serum IgE, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from two families who had similar syndromic features were studied. Thorough clinical evaluations, including brain MRI and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T cell cytokine production were measured. Whole exome sequencing was performed to identify disease-causing mutations. Immunoblotting, qRT-PCR, enzymatic assays, nucleotide sugar and sugar phosphate analyses along with MALDI-TOF mass spectrometry of glycans were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH2 and TH17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T cell lymphopenia, particularly of CD8+ T cells, and reduced memory B cells. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurological abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced UDP-GlcNAc, along with decreased O- and N-linked protein glycosylation in patients’ cells. These results define a new Congenital Disorder of Glycosylation. Conclusions Autosomal recessive, hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability and hypomyelination. PMID:24589341

  8. Additional case of Marden-Walker syndrome: support for the autosomal-recessive inheritance adn refinement of phenotype in a surviving patient. (United States)

    Orrico, A; Galli, L; Zappella, M; Orsi, A; Hayek, G


    In this report, we present a 14-year-old girl, born to consanguineous parents, who presented with severe mental retardation, hypotonia, short stature, and congenital joint contractures. The craniofacial features were scaphocephaly, thin/long and immobile face, marked hypoplasia of the midface, temporal narrowness, blepharophimosis, palpebral ptosis, and strabismus. The combination of such a distinctive craniofacial appearance and psychomotor retardation allows us to recognize a new case of the Marden-Walker syndrome. Our patient represents one of the rare cases in which consanguineous mating supports the autosomal-recessive pattern of inheritance of this condition. Furthermore, through refining the phenotype of a surviving patient, this report may contribute to a better recognition of this disorder in older affected children.

  9. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone- shaped epiphyses in hands and hips

    NARCIS (Netherlands)

    Hellemans, J; Coucke, PJ; Giedion, A; De Paepe, A; Kramer, P; Beemer, F; Mortier, GR


    Acrocapitofemoral dysplasia is a recently delineated autosomal recessive skeletal dysplasia, characterized clinically by short stature with short limbs and radiographically by cone-shaped epiphyses, mainly in hands and hips. Genome-wide homozygosity mapping in two consanguineous families linked the

  10. Autosomal recessive hypophosphataemic rickets with hypercalciuria is not caused by mutations in the type II renal sodium/phosphate cotransporter gene.

    NARCIS (Netherlands)

    Heuvel, L.P.W.J. van den; Koul, K. Op de; Knots, E.; Knoers, N.V.A.M.; Monnens, L.A.H.


    BACKGROUND: At present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (HHRH) is unknown. Type II sodium/phosphate cotransporter (NPT2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and a

  11. An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy (United States)

    Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido


    Purpose To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Methods Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. Results The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron–exon junction, we observed a homozygous 10 bp deletion between positions −26 and −17 (c.2281–26_-17del). The deletion was linked to a known SNP, c.2281–6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281–26_-17del leads to

  12. Mutation in LIM2 Is Responsible for Autosomal Recessive Congenital Cataracts (United States)

    Irum, Bushra; Khan, Shahid Y.; Ali, Muhammad; Kaul, Haiba; Kabir, Firoz; Rauf, Bushra; Fatima, Fareeha; Nadeem, Raheela; Khan, Arif O.; Al Obaisi, Saif; Naeem, Muhammad Asif; Nasir, Idrees A.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Akram, Javed; Eghrari, Allen O.; Riazuddin, S. Amer


    Purpose To identify the molecular basis of non-syndromic autosomal recessive congenital cataracts (arCC) in a consanguineous family. Methods All family members participating in the study received a comprehensive ophthalmic examination to determine their ocular phenotype and contributed a blood sample, from which genomic DNA was extracted. Available medical records and interviews with the family were used to compile the medical history of the family. The symptomatic history of the individuals exhibiting cataracts was confirmed by slit-lamp biomicroscopy. A genome-wide linkage analysis was performed to localize the disease interval. The candidate gene, LIM2 (lens intrinsic membrane protein 2), was sequenced bi-directionally to identify the disease-causing mutation. The physical changes caused by the mutation were analyzed in silico through homology modeling, mutation and bioinformatic algorithms, and evolutionary conservation databases. The physiological importance of LIM2 to ocular development was assessed in vivo by real-time expression analysis of Lim2 in a mouse model. Results Ophthalmic examination confirmed the diagnosis of nuclear cataracts in the affected members of the family; the inheritance pattern and cataract development in early infancy indicated arCC. Genome-wide linkage analysis localized the critical interval to chromosome 19q with a two-point logarithm of odds (LOD) score of 3.25. Bidirectional sequencing identified a novel missense mutation, c.233G>A (p.G78D) in LIM2. This mutation segregated with the disease phenotype and was absent in 192 ethnically matched control chromosomes. In silico analysis predicted lower hydropathicity and hydrophobicity but higher polarity of the mutant LIM2-encoded protein (MP19) compared to the wild-type. Moreover, these analyses predicted that the mutation would disrupt the secondary structure of a transmembrane domain of MP19. The expression of Lim2, which was detected in the mouse lens as early as embryonic day 15

  13. A pedigree-analysis approach to the descriptive epidemiology of autosomal-recessive disorders. (United States)

    Man, W Y N; Nicholas, F W; James, J W


    We describe a pedigree-analysis approach to estimating descriptive epidemiological parameters for autosomal-recessive disorders when the ancestral source of the disorder is known. We show that the expected frequency of carriers in a cohort equals the gene contribution of the ancestral source to that cohort, which is equivalent to the direct (additive) genetic relationship of that ancestor to the cohort. Also, the expected incidence of affected foetuses ranges from (1/2)F* to F*, where F* is the mean partial inbreeding coefficient (due to the ancestor) of the cohort. We applied this approach to complex vertebral malformation (CVM) in Holstein-Friesians in Australia, for which the ancestral source is a USA-born bull, Carlin-M Ivanhoe Bell. The estimated frequency of carriers was 2.47% for the 1992-born and 4.44% for the 1997-born cohort of Holstein-Friesian cows in Australia. The estimated incidence of affected foetuses/calves was considerably less than one per thousand, ranging from 0.0024 to 0.0048% for the 1992-born cohort, and from 0.0288 to 0.0576% for the 1997-born cohort. These incidences correspond to expected numbers of affected female foetuses/calves ranging from 2 to 4 for the 1992-born cohort and from 28 to 56 for the 1997-born cohort. This approach is easy to implement using software that is readily available.

  14. Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism

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    Takakuwa Koichi


    Full Text Available Abstract Background Pregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2. Case presentation A 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years. Conclusion Pregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.

  15. Mutations in Transglutaminase 1 Gene in Autosomal Recessive Congenital Ichthyosis in Egyptian Families

    Directory of Open Access Journals (Sweden)

    R. M. Shawky


    Full Text Available Autosomal recessive congenital ichthyosis (ARCI is a rare heterogeneous keratinization disorder of the skin. It is clinically divided into 2 subtypes, lamellar ichthyosis (LI and congenital ichthyosiformis erythroderma (CIE. We investigated forty-three ARCI Egyptian individuals in 16 severe LI, and 10 CIE families. We identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by the MspI restriction endonuclease. This promoted to a frequency of 9.6% for this mutation (5 splice-mutation alleles/52 alleles tested. We extended our previous dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52, whereas we still had no R141H among our Egyptian population. There was no correlation between phenotype and genotype in our study. Surprisingly, the mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form. We clearly demonstrated that the ARCI Egyptian families in Upper Egypt was ethnically pure and had a tendency not to be a hybrid with other populations in Lower Egypt, Delta zone and Cairo city.

  16. Development of novel noninvasive prenatal testing protocol for whole autosomal recessive disease using picodroplet digital PCR (United States)

    Chang, Mun Young; Kim, Ah Reum; Kim, Min Young; Kim, Soyoung; Yoon, Jinsun; Han, Jae Joon; Ahn, Soyeon; Kang, Changsoo; Choi, Byung Yoon


    We developed a protocol of noninvasive prenatal testing (NIPT), employing a higher-resolution picodroplet digital PCR, to detect genetic imbalance in maternal plasma DNA (mpDNA) caused by cell-free fetal DNA (cffDNA). In the present study, this approach was applied to four families with autosomal recessive (AR) congenital sensorineural hearing loss. First, a fraction of the fetal DNA in mpDNA was calculated. Then, we made artificial DNA mixtures (positive and negative controls) to simulate mpDNA containing the fraction of cffDNA with or without mutations. Next, a fraction of mutant cluster signals over the total signals was measured from mpDNA, positive controls, and negative controls. We determined whether fetal DNA carried any paternal or maternal mutations by calculating and comparing the sum of the log-likelihood of the study samples. Of the four families, we made a successful prediction of the complete fetal genotype in two cases where a distinct cluster was identified for each genotype and the fraction of cffDNA in mpDNA was at least 6.4%. Genotyping of only paternal mutation was possible in one of the other two families. This is the first NIPT protocol potentially applicable to any AR monogenic disease with various genotypes, including point mutations. PMID:27924908

  17. Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa. (United States)

    Perez-Carro, Raquel; Corton, Marta; Sánchez-Navarro, Iker; Zurita, Olga; Sanchez-Bolivar, Noelia; Sánchez-Alcudia, Rocío; Lelieveld, Stefan H; Aller, Elena; Lopez-Martinez, Miguel Angel; López-Molina, Ma Isabel; Fernandez-San Jose, Patricia; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Gilissen, Christian; Millan, Jose M; Avila-Fernandez, Almudena; Ayuso, Carmen


    Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis.

  18. The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease. (United States)

    Goto, Miwa; Hoxha, Nita; Osman, Rania; Dell, Katherine Macrae


    Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.

  19. Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies? (United States)

    Straub, Volker; Bertoli, Marta


    Autosomal recessive limb girdle muscular dystrophies (LGMD2) are a group of genetically heterogeneous diseases that are typically characterised by progressive weakness and wasting of the shoulder and pelvic girdle muscles. Many of the more than 20 different conditions show overlapping clinical features with other forms of muscular dystrophy, congenital, myofibrillar or even distal myopathies and also with acquired muscle diseases. Although individually extremely rare, all types of LGMD2 together form an important differential diagnostic group among neuromuscular diseases. Despite improved diagnostics and pathomechanistic insight, a curative therapy is currently lacking for any of these diseases. Medical care consists of the symptomatic treatment of complications, aiming to improve life expectancy and quality of life. Besides well characterised pre-clinical tools like animal models and cell culture assays, the determinants of successful drug development programmes for rare diseases include a good understanding of the phenotype and natural history of the disease, the existence of clinically relevant outcome measures, guidance on care standards, up to date patient registries, and, ideally, biomarkers that can help assess disease severity or drug response. Strong patient organisations driving research and successful partnerships between academia, advocacy, industry and regulatory authorities can also help accelerate the elaboration of clinical trials. All these determinants constitute aspects of translational research efforts and influence patient access to therapies. Here we review the current status of determinants of successful drug development programmes for LGMD2, and the challenges of translating promising therapeutic strategies into effective and accessible treatments for patients.

  20. Mutation Spectrum of EYS in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa (United States)

    Barragán, Isabel; Borrego, Salud; Pieras, Juan Ignacio; Pozo, María González-del; Santoyo, Javier; Ayuso, Carmen; Baiget, Montserrat; Millan, José M; Mena, Marcela; El-Aziz, Mai M Abd; Audo, Isabelle; Zeitz, Christina; Littink, Karin W; Dopazo, Joaquín; Bhattacharya, Shomi S; Antiñolo, Guillermo


    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding an ortholog of Drosophila spacemaker (spam) as a commonly mutated gene in autosomal recessive RP. In the present study, we report the identification of 73 sequence variations in EYS, of which 28 are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28) are possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have detected 3 pathogenic changes previously reported in other populations. We are also presenting the characterisation of EYS homologues in different species, and a detailed analysis of the EYS domains, with the identification of an interesting novel feature: a putative coiled-coil domain. Majority of the mutations in the arRP patients have been found within the domain structures of EYS. The minimum observed prevalence of distinct EYS mutations in our group of patients is of 15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP in the Spanish population. Along with the detection of three recurrent mutations in Caucasian population, our hypothesis of EYS being the first prevalent gene in arRP has been reinforced in the present study. © 2010 Wiley-Liss, Inc. PMID:21069908

  1. Libyan Boy with Autosomal Recessive Trait (P22-phox Defect of Chronic Granulomatous Disease

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    Ilka Schulze


    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes cannot produce active oxygen metabolites, and therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs.In this report, we present a boy from Libya with a rare autosomal recessive trait of CGD (defect of p22-phox who has chronic lung disease following multiple severe pneumonia attacks. The case we present suffered from bloody diarrhea since the third month of his life. He also had recurrent episodes of fever, and later, developed persistent cervical lymphadenitis and failure to gain weight. CGD is a very rare condition worldwide. It is also not recognized here in Libya, and usually not in the list of differential diagnosis for chronic pulmonary infections. We advise that pediatricians and general practitioners who treat chronic cases of lung diseases (with or without chronic diarrhea should consider primary immunodeficiency disorders in the hope that early diagnosis and treatment may prevent chronic complications especially of the respiratory tract. Furthermore, we state that, to the best of our knowledge, this is the first documented case of CGD from Libya.

  2. The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel. (United States)

    Zlotogora, Joël


    The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze In the last decade, data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database ( ). In the non-Jewish population, up to 1 July 2010, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria and congenital adrenal hyperplasia, as well as data on 195 autosomal recessive diseases among Muslim Israeli Arabs, 11 among the Christian Arabs and 31 among Druze. A single mutation was characterized in 149 out of the 238 rare disorders for which the molecular basis was known. In many diseases, mutation had never been observed in any other population and was present in one family only suggesting that it occurred as a de novo event. In other diseases, the mutation was present in more than one community or even in other populations such as Bedouins from the Arab peninsula or Christians from Lebanon. In the 89 other disorders, more than one mutation was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases such as Bardet Biedl among the Bedouins, the reason may be a selective advantage to the heterozygotes.

  3. A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability

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    Ali Nadir


    Full Text Available Abstract Background Intellectual disability (ID is a serious disorder of the central nervous system with a prevalence of 1-3% in a general population. In the past decades, the research focus has been predominantly on X-linked ID (68 loci and 19 genes for non syndromic X linked ID while for autosomal recessive nonsyndromic ID (NSID only 30 loci and 6 genes have been reported to date. Methods Genome-wide homozygosity mapping with 500 K Nsp1 array (Affymetrix, CNV analysis, PCR based breakpoint mapping and DNA sequencing was performed to explore the genetic basis of autosomal recessive nonsyndromic ID in a large Pakistani family. Results Data analysis showed linkage at 8p23 locus with common homozygous region between SNPs rs6989820 and rs2237834, spanning a region of 12.494 Mb. The subsequent CNV analysis of the data revealed a homozygous deletion of 170.673 Kb which encompassed the TUSC3 gene. Conclusion We report a novel deletion mutation in TUSC3 gene which is the second gene after TRAPPC9 in which mutation has been identified in more than one family with autosomal recessive NSID. The study will aid in exploring the molecular pathway of cognition.

  4. Proof-of-principle rapid noninvasive prenatal diagnosis of autosomal recessive founder mutations (United States)

    Zeevi, David A.; Altarescu, Gheona; Weinberg-Shukron, Ariella; Zahdeh, Fouad; Dinur, Tama; Chicco, Gaya; Herskovitz, Yair; Renbaum, Paul; Elstein, Deborah; Levy-Lahad, Ephrat; Rolfs, Arndt; Zimran, Ari


    BACKGROUND. Noninvasive prenatal testing can be used to accurately detect chromosomal aneuploidies in circulating fetal DNA; however, the necessity of parental haplotype construction is a primary drawback to noninvasive prenatal diagnosis (NIPD) of monogenic disease. Family-specific haplotype assembly is essential for accurate diagnosis of minuscule amounts of circulating cell-free fetal DNA; however, current haplotyping techniques are too time-consuming and laborious to be carried out within the limited time constraints of prenatal testing, hampering practical application of NIPD in the clinic. Here, we have addressed this pitfall and devised a universal strategy for rapid NIPD of a prevalent mutation in the Ashkenazi Jewish (AJ) population. METHODS. Pregnant AJ couples, carrying mutation(s) in GBA, which encodes acid β-glucosidase, were recruited at the SZMC Gaucher Clinic. Targeted next-generation sequencing of GBA-flanking SNPs was performed on peripheral blood samples from each couple, relevant mutation carrier family members, and unrelated individuals who are homozygotes for an AJ founder mutation. Allele-specific haplotypes were constructed based on linkage, and a consensus Gaucher disease–associated founder mutation–flanking haplotype was fine mapped. Together, these haplotypes were used for NIPD. All test results were validated by conventional prenatal or postnatal diagnostic methods. RESULTS. Ten parental alleles in eight unrelated fetuses were diagnosed successfully based on the noninvasive method developed in this study. The consensus mutation–flanking haplotype aided diagnosis for 6 of 9 founder mutation alleles. CONCLUSIONS. The founder NIPD method developed and described here is rapid, economical, and readily adaptable for prenatal testing of prevalent autosomal recessive disease-causing mutations in an assortment of worldwide populations. FUNDING. SZMC, Protalix Biotherapeutics Inc., and Centogene AG. PMID:26426075

  5. Brain Connectivity Changes in Autosomal Recessive Parkinson Disease: A Model for the Sporadic Form (United States)

    Makovac, Elena; Cercignani, Mara; Serra, Laura; Torso, Mario; Spanò, Barbara; Petrucci, Simona; Ricciardi, Lucia; Ginevrino, Monia; Caltagirone, Carlo; Bentivoglio, Anna Rita; Valente, Enza Maria; Bozzali, Marco


    Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients’ cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptoms. PMID:27788143

  6. Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts (United States)

    Irum, Bushra; Khan, Shahid Y.; Ali, Muhammad; Daud, Muhammad; Kabir, Firoz; Rauf, Bushra; Fatima, Fareeha; Iqbal, Hira; Khan, Arif O.; Al Obaisi, Saif; Naeem, Muhammad Asif; Nasir, Idrees A.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Akram, Javed; Eghrari, Allen O.; Riazuddin, S. Amer


    Purpose The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree. Methods All participating individuals underwent a detailed ophthalmic examination. Each patient’s medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA. Genetic analysis was performed to rule out linkage to known arCC loci and genes. Whole-exome sequencing libraries were prepared and paired-end sequenced. A large deletion was found that segregated with arCC in the family, and chromosome walking was conducted to estimate the proximal and distal boundaries of the deletion mutation. Results Exclusion and linkage analysis suggested linkage to a region of chromosome 6p24 harboring GCNT2 (glucosaminyl (N-acetyl) transferase 2) with a two-point logarithm of odds score of 5.78. PCR amplifications of the coding exons of GCNT2 failed in individuals with arCC, and whole-exome data analysis revealed a large deletion on chromosome 6p in the region harboring GCNT2. Chromosomal walking using multiple primer pairs delineated the extent of the deletion to approximately 190 kb. Interestingly, a failure to amplify a junctional fragment of the deletion break strongly suggests an insertion in addition to the large deletion. Conclusion Here, we report a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family. PMID:27936067

  7. Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. (United States)

    El-Sayed, Walid; Parry, David A; Shore, Roger C; Ahmed, Mushtaq; Jafri, Hussain; Rashid, Yasmin; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J


    Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative beta propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation.

  8. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects. (United States)

    Zhang, Jinglan; Lachance, Véronik; Schaffner, Adam; Li, Xianting; Fedick, Anastasia; Kaye, Lauren E; Liao, Jun; Rosenfeld, Jill; Yachelevich, Naomi; Chu, Mary-Lynn; Mitchell, Wendy G; Boles, Richard G; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Bagley, Kaytee; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa


    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.

  9. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.

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    Jinglan Zhang


    Full Text Available Genetic leukoencephalopathies (gLEs are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS. The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES, we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G, as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026. VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting and CORVET (class C core vacuole/endosome tethering protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.

  10. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects (United States)

    Schaffner, Adam; Fedick, Anastasia; Kaye, Lauren E.; Liao, Jun; Yachelevich, Naomi; Chu, Mary-Lynn; Boles, Richard G.; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A.; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa


    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway. PMID:27120463

  11. A Register-Based Study of Diseases With an Autosomal Recessive Origin in Small Children in Denmark According to Maternal Country of Origin

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    Gundlund, Anna; Hansen, Anne Vinkel; Pedersen, Grete Skøtt


    information on consanguinity is lacking, this suggestion is difficult to test. With an indirect approach, we addressed this question by comparing the risk of diseases with autosomal recessive inheritance in children born in Denmark of Danish-born women and of women born in these five countries, respectively....... METHODS: All children born in Denmark (1994-2010) were followed until 5 years of age or end-of-study period for the risk of hospitalisation with diseases of autosomal recessive aetiology, and therefore considered consanguinity-related. Diagnoses of autosomal recessive diseases were identified using two...... different methods: a literature review of consanguinity-associated diseases and a search in the Online Catalogue of Human Genes and Genetic Disorders. Risks were also calculated for diseases with known non-autosomal recessive aetiology (considered non-consanguinity-related). We estimated adjusted hazard...

  12. Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families.

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    Sobia Shafique

    Full Text Available The frequency of inherited bilateral autosomal recessive non-syndromic hearing loss (ARNSHL in Pakistan is 1.6/1000 individuals. More than 50% of the families carry mutations in GJB2 while mutations in MYO15A account for about 5% of recessive deafness. In the present study a cohort of 30 ARNSHL families was initially screened for mutations in GJB2 and MYO15A. Homozygosity mapping was performed by employing whole genome single nucleotide polymorphism (SNP genotyping in the families that did not carry mutations in GJB2 or MYO15A. Mutation analysis was performed for the known ARNSHL genes present in the homozygous regions to determine the causative mutations. This allowed the identification of a causative mutation in all the 30 families including 9 novel mutations, which were identified in 9 different families (GJB2 (c.598G>A, p.Gly200Arg; MYO15A (c.9948G>A, p.Gln3316Gln; c.3866+1G>A; c.8767C>T, p.Arg2923* and c.8222T>C, p.Phe2741Ser, TMC1 (c.362+18A>G, BSND (c.97G>C, p.Val33Leu, TMPRSS3 (c.726C>G, p.Cys242Trp and MSRB3 (c.20T>G, p.Leu7Arg. Furthermore, 12 recurrent mutations were detected in 21 other families. The 21 identified mutations included 10 (48% missense changes, 4 (19% nonsense mutations, 3 (14% intronic mutations, 2 (9% splice site mutations and 2 (9% frameshift mutations. GJB2 accounted for 53% of the families, while mutations in MYO15A were the second most frequent (13% cause of ARNSHL in these 30 families. The identification of novel as well as recurrent mutations in the present study increases the spectrum of mutations in known deafness genes which could lead to the identification of novel founder mutations and population specific mutated deafness genes causative of ARNSHL. These results provide detailed genetic information that has potential diagnostic implication in the establishment of cost-efficient allele-specific analysis of frequently occurring variants in combination with other reported mutations in Pakistani populations.

  13. A novel frameshift mutation in KCNQ4 in a family with autosomal recessive non-syndromic hearing loss. (United States)

    Wasano, Koichiro; Mutai, Hideki; Obuchi, Chie; Masuda, Sawako; Matsunaga, Tatsuo


    Mutation of KCNQ4 has been reported to cause autosomal dominant non-syndromic hearing loss (DFNA2A) that usually presents as progressive hearing loss starting from mild to moderate hearing loss during childhood. Here, we identified a novel KCNQ4 mutation, c.1044_1051del8, in a family with autosomal recessive non-syndromic hearing loss. The proband was homozygous for the mutation and was born to consanguineous parents; she showed severe hearing loss that was either congenital or of early childhood onset. The proband had a sister who was heterozygous for the mutation but showed normal hearing. The mutation caused a frameshift that eliminated most of the cytoplasmic C-terminus, including the A-domain, which has an important role for protein tetramerization, and the B-segment, which is a binding site for calmodulin (CaM) that regulates channel function via Ca ions. The fact that the heterozygote had normal hearing indicates that sufficient tetramerization and CaM binding sites were present to preserve a normal phenotype even when only half the proteins contained an A-domain and B-segment. On the other hand, the severe hearing loss in the homozygote suggests that complete loss of the A-domain and B-segment in the protein caused loss of function due to the failure of tetramer formation and CaM binding. This family suggests that some KCNQ4 mutations can cause autosomal recessive hearing loss with more severe phenotype in addition to autosomal dominant hearing loss with milder phenotype. This genotype-phenotype correlation is analogous to that in KCNQ1 which causes autosomal dominant hereditary long QT syndrome 1 with milder phenotype and the autosomal recessive Jervell and Lange-Nielsen syndrome 1 with more severe phenotype due to deletion of the cytoplasmic C-terminus of the potassium channel.

  14. A mutation in the FOXE3 gene causes congenital primary aphakia in an autosomal recessive consanguineous Pakistani family

    DEFF Research Database (Denmark)

    Anjum, Iram; Eiberg, Hans; Baig, Shahid Mahmood;


    PURPOSE: Aphakia is the complete absence of any lens in the eye, either due to surgical removal of the lens as a result of a perforating wound or ulcer, or due to a congenital anomaly. The purpose of this study was to elucidate the molecular genetics for a large consanguineous Pakistani family...... with a clear aphakia phenotype. METHODS: The initial homozygosity screening of the family was extended to all the known autosomal recessive cataract loci in order to exclude the possibility of surgical cataract removal leading to aphakia. The screening was performed using polymorphic nucleotide repeat markers...

  15. Arthrogryposis multiplex with deafness, inguinal hernias, and early death: a family report of a probably autosomal recessive trait. (United States)

    Tiemann, Christian; Bührer, Christoph; Burwinkel, Barbara; Wirtenberger, Michael; Hoehn, Thomas; Hübner, Christoph; van Landeghem, Frank K H; Stoltenburg, Gisela; Obladen, Michael


    We report on three male newborn infants of a highly inbred Lebanese family presenting with a characteristic phenotype: arthrogryposis multiplex, deafness, large inguinal hernia, hiccup-like diaphragmatic contractions, and inability to suck, requiring nasogastric gavage feeding. All three boys died from respiratory failure during the first 3 months of life. Intra vitam or post mortem examinations revealed myopathic changes and elevated glycogen content of muscle tissue. This new syndrome is probably transmitted in an autosomal recessive mode, although X-linked inheritance cannot be excluded.

  16. Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review. (United States)

    Tan, Christopher A; Rabideau, Marina; Blevins, Amy; Westbrook, Marjorie Jody; Ekstein, Tali; Nykamp, Keith; Deucher, Anne; Harper, Amy; Demmer, Laurie


    Pathogenic variants in the mitofusin 2 gene (MFN2) are the most common cause of autosomal dominant Charcot-Marie-Tooth (CMT2) disease, which is typically characterized by axonal sensorimotor neuropathy. We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2. A review of the literature reveals that sporadic and familial cases of compound heterozygous or homozygous pathogenic MFN2 variants have been infrequently described, which indicates that MFN2 can also be inherited in a recessive manner. This case highlights several clinical findings not typically associated with MFN2 pathogenic variants, including young age of onset and rapidly progressing diaphragmatic paresis that necessitated tracheostomy and mechanical ventilation, and adds to the growing list of features identified in autosomal recessive MFN2-related CMT2. Our patient with MFN2-related CMT2 expands the clinical and mutational spectrum of individuals with autosomal recessive CMT2 and identifies a new clinical feature that warrants further observation. © 2016 Wiley Periodicals, Inc.

  17. Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica

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    Ariana Kariminejad


    Full Text Available Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A, cutis laxa IIB (ARCL2B, and geroderma osteodysplastica (GO, have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient’s clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.

  18. A novel HSF4 gene mutation (p.R405X causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan

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    Cheema Abdul


    Full Text Available Abstract Background Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667. Here, we describe a family from Pakistan with the first nonsense mutation in HSF4 thus expanding the mutational spectrum of this heat shock transcription factor gene. Methods A large consanguineous Pakistani family with autosomal recessive cataracts was collected from Quetta. Genetic linkage analysis was performed for the common known autosomal recessive cataracts loci and linkage to a locus containing HSF4 (OMIM 602438 was found. All exons and adjacent splice sites of the heat shock transcription factor 4 gene (HSF4 were sequenced. A mutation-specific restriction enzyme digest (HphI was performed for all family members and unrelated controls. Results The disease phenotype perfectly co-segregated with markers flanking the known cataract gene HSF4, whereas other autosomal recessive loci were excluded. A maximum two-point LOD score with a Zmax = 5.6 at θ = 0 was obtained for D16S421. Direct sequencing of HSF4 revealed the nucleotide exchange c.1213C > T in this family predicting an arginine to stop codon exchange (p.R405X. Conclusion We identified the first nonsense mutation (p.R405X in exon 11 of HSF4 in a large consanguineous Pakistani family with autosomal recessive cataract.

  19. Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance

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    Andrea Guala


    Full Text Available We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD and Transient Tachypnea of the Newborn (TTN, and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes or suggested for TTN (genes affecting lung liquid clearance. Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely.

  20. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia

    DEFF Research Database (Denmark)

    Roos, L; Fang, M; Dali, C;


    to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where...... three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented...... with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations....

  1. Familial clustering of unexplained transient respiratory distress in 12 newborns from three unrelated families suggests an autosomal-recessive inheritance. (United States)

    Guala, Andrea; Carrera, Paola; Pastore, Guido; Somaschini, Marco; Ancora, Gina; Faldella, Giacomo; De Filippi, Paolo; Ferrero, Federica; Guarino, Roberta; Danesino, Cesare


    We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely.

  2. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. (United States)

    Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna


    Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration.

  3. Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement.

    NARCIS (Netherlands)

    Estrada-Cuzcano, A.; Neveling, K.; Kohl, S.; Banin, E.; Rotenstreich, Y.; Sharon, D.; Falik-Zaccai, T.C.; Hipp, S.; Roepman, R.; Wissinger, B.; Letteboer, S.J.F.; Mans, D.A.; Blokland, E.A.W.; Kwint, M.P.; Gijsen, S.J.; Huet, R.A.C. van; Collin, R.W.J.; Scheffer, H.; Veltman, J.A.; Zrenner, E.; Hollander, A.I. den; Klevering, B.J.; Cremers, F.P.M.


    Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together

  4. A novel locus for autosomal recessive nonsyndromic hearing impairment, DFNB63, maps to chromosome 11q13.2-q13.4.

    NARCIS (Netherlands)

    Kalay, E.; Caylan, R.; Kiroglu, A.F.; Yasar, T.; Collin, R.W.J.; Heister, J.G.A.M.; Oostrik, J.; Cremers, C.W.R.J.; Brunner, H.G.; Karaguzel, A.; Kremer, H.


    Hereditary hearing impairment is a genetically heterogeneous disorder. To date, 49 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been described, and there are more than 16 additional loci announced. In 25 of the known loci, causative genes have been identified. A genome scan

  5. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease

    DEFF Research Database (Denmark)

    Gal, Andreas; Rau, Isabella; El Matri, Leila


    Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we...

  6. Microcefalia primária autossômica recessiva em três famílias pernambucanas: aspectos clínicos e moleculares Autosomal recessive primary microcephaly in three families from Pernambuco: clinical and molecular aspects

    Directory of Open Access Journals (Sweden)

    Gabriela F. Leal


    Full Text Available OBJETIVOS: descrever os aspectos clínicos de três famílias pernambucanas com microcefalia primária autossômica recessiva e as análises de ligação em uma delas (família 2. MÉTODOS: três famílias consangüíneas pernambucanas, não relacionadas biologicamente, com microcefalia primária, foram estudadas. Os heredogramas e a história clínica dos afetados foram construídos com base em informações obtidas de seus pais e outros parentes. O exame físico foi realizado em todos os afetados, seus genitores e na quase totalidade dos irmãos normais dos afetados. O DNA genômico dos afetados da família 2 e de seus pais foi usado em reações de PCR (polimerase chain reaction com primers elaborados para amplificar marcadores microssatélites ligados aos locos já conhecidos de microcefalia primária autossômica recessiva. Os marcadores amplificados foram submetidos a eletroforese e seus alelos analisados. RESULTADOS: nas três famílias, os afetados apresentavam perímetro cefálico muito reduzido acompanhado de retardo mental e apenas uma paciente (da família 3 manifestava outras alterações neurológicas, mas sem dismorfias associadas. Estudos moleculares demonstraram que a microcefalia, na família 2, não apresentava ligação com nenhum dos locos associados à microcefalia primária autossômica recessiva já conhecidos. CONCLUSÕES: pelo menos mais um gene associado à microcefalia primária autossômica recessiva existe e aguarda identificação.OBJECTIVES: to describe the clinical findings in three families from Pernambuco with autosomal recessive primary microcephaly, and the linkage analysis in one of them (family 2. METHODS: three consanguineous families from Pernambuco, not related one to another and with primary microcephaly, were studied. The genealogical data and the clinical history of the affected individuals were obtained from their parents and other family members. All the affected subjects, almost all their normal

  7. Novel Mutations and Mutation Combinations of TMPRSS3 Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment (United States)

    Wang, Guo-Jian; Xu, Jin-Cao; Su, Yu


    Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in the TMPRSS3 gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8). TMPRSS3 mutations can be classified as mild or severe, and the phenotype is dependent on the combination of TMPRSS3 mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milder TMPRSS3 mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations in TMPRSS3, one novel mutation c.36delC [p.(Phe13Serfs⁎12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs⁎12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs⁎12). We concluded that different combinations of TMPRSS3 mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family. PMID:28246597

  8. Autosomal recessive posterior column ataxia with retinitis pigmentosa caused by novel mutations in the FLVCR1 gene. (United States)

    Shaibani, Aziz; Wong, Lee-Jun; Wei Zhang, Victor; Lewis, Richard Alan; Shinawi, Marwan


    Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive disorder characterized by severe sensory ataxia, muscle weakness and atrophy, and progressive pigmentary retinopathy. Recently, mutations in the FLVCR1 gene were described in four families with this condition. We investigated the molecular basis and studied the phenotype of PCARP in a new family. The proband is a 33-year-old woman presented with sensory polyneuropathy and retinitis pigmentosa (RP). The constellation of clinical findings with normal metabolic and genetic evaluation, including mitochondrial DNA (mtDNA) analysis and normal levels of phytanic acid and vitamin E, prompted us to seek other causes of our patient's condition. Sequencing of FLVCR1 in the proband and targeted mutation testing in her two affected siblings revealed two novel variants, c.1547G > A (p.R516Q) and c.1593+5_+8delGTAA predicted, respectively, to be highly conserved throughout evolution and affecting the normal splicing, therefore, deleterious. This study supports the pathogenic role of FLVCR1 in PCARP and expands the molecular and clinical spectra of PCARP. We show for the first time that nontransmembrane domain (TMD) mutations in the FLVCR1 can cause PCARP, suggesting different mechanisms for pathogenicity. Our clinical data reveal that impaired sensation can be part of the phenotypic spectrum of PCARP. This study along with previously reported cases suggests that targeted sequencing of the FLVCR1 gene should be considered in patients with severe sensory ataxia, RP, and peripheral sensory neuropathy.

  9. A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus. (United States)

    Christensen, J H; Kvistgaard, H; Knudsen, J; Shaikh, G; Tolmie, J; Cooke, S; Pedersen, S; Corydon, T J; Gregersen, N; Rittig, S


    Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.

  10. Linkage of autosomal recessive primary congenital glaucoma to the GLC3A locus in Roms (Gypsies) from Slovakia. (United States)

    Plásilová, M; Feráková, E; Kádasi, L; Poláková, H; Gerinec, A; Ott, J; Ferák, V


    The autosomal recessive form of primary congenital glaucoma (gene symbol GLC3) has been recently mapped to two different loci, GLC3A (at 2p21), and GLC3B (at 1p36), respectively, on families of Turkish and Saudi Arabian provenance. This disorder is known to occur with an extremely high incidence in Roms (Gypsies) in Slovakia. We performed a standard linkage analysis on a sample of 7 Slovak Gypsy families comprising 18 affected members, and found significant linkage with four STR markers from the chromosomal region of 2p21 (D2S1788, D2S1346, D2S2328, and D2S1356), without heterogeneity. This finding demonstrates that in the Rom population of Slovakia, primary congenital glaucoma is due to the locus GLC3A, and consequently, to the mutation(s) in the cytochrome P4501B1 gene, which has been recently identified as the principal cause of the disease. Roms represent the third population, in which the disorder has been mapped to GLC3A.

  11. Preimplantation genetic diagnosis for a Chinese family with autosomal recessive Meckel-Gruber syndrome type 3 (MKS3.

    Directory of Open Access Journals (Sweden)

    Yanping Lu

    Full Text Available Meckel-Gruber syndrome type 3 is an autosomal recessive genetic defect caused by mutations in TMEM67 gene. In our previous study, we have identified a homozygous TMEM67 mutation in a Chinese family exhibiting clinical characteristics of MKS3, which provided a ground for further PGD procedure. Here we report the development and the first clinical application of the PGD for this MKS3 family. Molecular analysis protocol for clinical PGD procedure was established using 50 single cells in pre-clinical set-up. After whole genomic amplification by multiple displacement amplification with the DNA from single cells, three techniques were applied simultaneously to increase the accuracy and reliability of genetic diagnosis in single blastomere, including real-time PCR with Taq Man-MGB probe, haplotype analysis with polymorphic STR markers and Sanger sequencing. In the clinical PGD cycle, nine embryos at cleavage-stage were biopsied and subjected to genetic diagnosis. Two embryos diagnosed as free of TMEM67 mutation were transferred and one achieving normal pregnancy. Non-invasive prenatal assessment of trisomy 13, 18 and 21 by multiplex DNA sequencing at 18 weeks' gestation excluded the aneuploidy of the analyzed chromosomes. A healthy boy was delivered by cesarean section at 39 weeks' gestation. DNA sequencing from his cord blood confirmed the result of genetic analysis in the PGD cycle. The protocol developed in this study was proved to be rapid and safe for the detection of monogenic mutations in clinical PGD cycle.

  12. Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27

    Energy Technology Data Exchange (ETDEWEB)

    Matsumine, Hiroto; Shimoda-Matsubayashi, Satoe; Nakagawa-Hattori, Yuko [Tokyo Metropolitan Ebara Hospital (Japan)] [and others


    An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 ({theta} = .03) and D6S253 ({theta} = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons. 38 refs., 4 figs., 1 tab.

  13. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability (United States)

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J. M.; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D. James; Carter, Melissa T.; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B.


    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. PMID:26206890

  14. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

    Directory of Open Access Journals (Sweden)

    Insa Bultmann-Mellin


    Full Text Available Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C, which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been discovered based on similar elastic fiber abnormalities exhibited by mice lacking the short Ltbp-4 isoform (Ltbp4S−/−, the murine phenotype does not replicate ARCL1C. We therefore inactivated both Ltbp-4 isoforms in the mouse germline to model ARCL1C. Comparative analysis of Ltbp4S−/− and Ltbp4-null (Ltbp4−/− mice identified Ltbp-4L as an important factor for elastogenesis and postnatal survival, and showed that it has distinct tissue expression patterns and specific molecular functions. We identified fibulin-4 as a previously unknown interaction partner of both Ltbp-4 isoforms and demonstrated that at least Ltbp-4L expression is essential for incorporation of fibulin-4 into the extracellular matrix (ECM. Overall, our results contribute to the current understanding of elastogenesis and provide an animal model of ARCL1C.

  15. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia. (United States)

    Roos, L; Fang, M; Dali, C; Jensen, H; Christoffersen, N; Wu, B; Zhang, J; Xu, R; Harris, P; Xu, X; Grønskov, K; Tümer, Z


    Anomalies of eye development can lead to the rare eye malformations microphthalmia and anophthalmia (small or absent ocular globes), which are genetically very heterogeneous. Several genes have been associated with microphthalmia and anophthalmia, and exome sequencing has contributed to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations.

  16. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A.; Hernandez, Dena G.; Heutink, Peter; Gibbs, J. Raphael; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Viallet, François; Brice, Alexis; Lesage, Suzanne; Majounie, Elisa; Tison, François; Vidailhet, Marie; Corvol, Jean Christophe; Nalls, Michael A.; Hernandez, Dena G.; Gibbs, J. Raphael; Dürr, Alexandra; Arepalli, Sampath; Barker, Roger A.; Ben-Shlomo, Yoav; Berg, Daniela; Bettella, Francesco; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bastiaan R.; Bochdanovits, Zoltan; Bonin, Michael; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Dong, Jing; Durif, Frank; Edkins, Sarah; Escott-Price, Valentina; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michèle; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Kilarski, Laura L.; Jansen, Iris E.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Lubbe, Steven; Lungu, Codrin; Martinez, María; Mätzler, Walter; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O’Sullivan, Sean S.; Owen, Michael J.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Simón-Sánchez, Javier; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Schulte, Claudia; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Shulman, Joshua; Sidransky, Ellen; Spencer, Chris C.A.; Stefánsson, Hreinn; Stefánsson, Kári; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wurster, Isabel; Williams, Nigel; Morris, Huw R.; Heutink, Peter; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Singleton, Andrew B.; Brice, Alexis


    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  17. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))


    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

  18. Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors. (United States)

    Navarro, Claire L; Cadiñanos, Juan; De Sandre-Giovannoli, Annachiara; Bernard, Rafaëlle; Courrier, Sébastien; Boccaccio, Irène; Boyer, Amandine; Kleijer, Wim J; Wagner, Anja; Giuliano, Fabienne; Beemer, Frits A; Freije, Jose M; Cau, Pierre; Hennekam, Raoul C M; López-Otín, Carlos; Badens, Catherine; Lévy, Nicolas


    Restrictive dermopathy (RD) is characterized by intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death. In two patients affected with RD, we recently reported two different heterozygous splicing mutations in the LMNA gene, leading to the production and accumulation of truncated Prelamin A. In other patients, a single nucleotide insertion was identified in ZMPSTE24. This variation is located in a homopolymeric repeat of thymines and introduces a premature termination codon. ZMPSTE24 encodes an endoprotease essential for the post-translational cleavage of the Lamin A precursor and the production of mature Lamin A. However, the autosomal recessive inheritance of RD suggested that a further molecular defect was present either in the second ZMPSTE24 allele or in another gene involved in Lamin A processing. Here, we report new findings in RD linked to ZMPSTE24 mutations. Ten RD patients were analyzed including seven from a previous series and three novel patients. All were found to be either homozygous or compound heterozygous for ZMPSTE24 mutations. We report three novel 'null' mutations as well as the recurrent thymine insertion. In all cases, we find a complete absence of both ZMPSTE24 and mature Lamin A associated with Prelamin A accumulation. Thus, RD is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations, most of which lie in a mutation hotspot within exon 9. The accumulation of truncated or normal length Prelamin A is, therefore, a shared pathophysiological feature in recessive and dominant RD. These findings have an important impact on our knowledge of the pathophysiology in Progeria and related disorders and will help direct the development of therapeutic approaches.

  19. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

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    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  20. Analysis of missense variants in the PKHD1-gene in patients with autosomal recessive polycystic kidney disease (ARPKD). (United States)

    Losekoot, Monique; Haarloo, Cathleen; Ruivenkamp, Claudia; White, Stefan J; Breuning, Martijn H; Peters, Dorien J M


    Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease characterized by enlarged kidneys and congenital hepatic fibrosis. Given the poor prognosis for the majority of children with the severe perinatal ARPKD phenotype, there is a regular request for prenatal testing. ARPKD is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene, which consists of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest transcript, comprising 67 exons, encodes the protein fibrocystin/polyductin. We have set up mutation analysis by direct sequencing of these 67 exons. In 39 mainly Dutch families we identified: 11 nonsense mutations, 15 deletions/insertions, 5 splice site mutations, and 39 missense mutations. To classify missense variants we combined evolutionary conservation, using the human, chimpanzee, dog, mouse, chicken and frog Pkhd1 sequences, with the Grantham score for chemical differences. Thirty-three missense mutations were considered pathogenic and seven were classified as rare, probably pathogenic variants. In addition to sequence analysis, multiplex ligation-dependent probe amplification (MLPA) was used to identify multiple exon deletions. However, no large deletions in the PKHD1 gene were identified. In 31 index patients two mutations were found, in 6 patients one mutation was found, leading to a mutation detection rate of 87%. The analysis of amino acid conservation as well as applying the Grantham score for chemical differences allowed us to determine the pathogeneity for nearly all new missense mutations and thus proved to be useful tools to classify missense variants.

  1. Autosomal recessive ataxias: 20 types, and counting Ataxias autossômicas recessivas: 20 tipos e muito mais

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    Emília Katiane Embiruçu


    Full Text Available More than 140 years after the first description of Friedreich ataxia, autosomal recessive ataxias have become one of the more complex fields in Neurogenetics. Currently this group of diseases contains more than 20 clinical entities and an even larger number of associated genes. Some disorders are very rare, restricted to isolated populations, and others are found worldwide. An expressive number of recessive ataxias are treatable, and responsibility for an accurate diagnosis is high. The purpose of this review is to update the practitioner on clinical and pathophysiological aspects of these disorders and to present an algorithm to guide the diagnosis.Mais de 140 anos após a primeira descrição da ataxia de Friedreich, as ataxias autossômicas recessivas se transformaram em um dos mais complexos campos da Neurogenética. Atualmente, este grupo de doenças é composto por mais de 20 entidades clínicas e possui um número ainda maior de genes associados. Algumas doenças são muito raras, tendo sido observadas apenas em populações isoladas, enquanto que outras são encontradas no mundo todo. Um número expressivo de ataxias é tratável, e a responsabilidade em se fazer um diagnóstico correto é alta. A finalidade desta revisão é a de atualizar o neurologista a respeito dos principais aspectos clínicos e fisiopatológicos destas doenças e de apresentar um algoritmo para auxiliar a sua investigação e o seu diagnóstico.

  2. Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes. (United States)

    Büscher, Rainer; Büscher, Anja K; Weber, Stefanie; Mohr, Julia; Hegen, Bianca; Vester, Udo; Hoyer, Peter F


    Autosomal recessive polycystic kidney disease (ARPKD), although less frequent than the dominant form, is a common, inherited ciliopathy of childhood that is caused by mutations in the PKHD1-gene on chromosome 6. The characteristic dilatation of the renal collecting ducts starts in utero and can present at any stage from infancy to adulthood. Renal insufficiency may already begin in utero and may lead to early abortion or oligohydramnios and lung hypoplasia in the newborn. However, there are also affected children who have no evidence of renal dysfunction in utero and who are born with normal renal function. Up to 30 % of patients die in the perinatal period, and those surviving the neonatal period reach end stage renal disease (ESRD) in infancy, early childhood or adolescence. In contrast, some affected patients have been diagnosed as adults with renal function ranging from normal to moderate renal insufficiency to ESRD. The clinical spectrum of ARPKD is broader than previously recognized. While bilateral renal enlargement with microcystic dilatation is the predominant clinical feature, arterial hypertension, intrahepatic biliary dysgenesis remain important manifestations that affect approximately 45 % of infants. All patients with ARPKD develop clinical findings of congenital hepatic fibrosis (CHF); however, non-obstructive dilation of the intrahepatic bile ducts in the liver (Caroli's disease) is seen at the histological level in only a subset of patients. Cholangitis and variceal bleeding, sequelae of portal hypertension, are life-threatening complications that may occur more often in advanced cases of liver disease. In this review we focus on common and uncommon kidney-related and non-kidney-related phenotypes. Clinical management of ARPKD patients should include consideration of potential problems related to these manifestations.

  3. Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. (United States)

    Zeitz, Christina; Jacobson, Samuel G; Hamel, Christian P; Bujakowska, Kinga; Neuillé, Marion; Orhan, Elise; Zanlonghi, Xavier; Lancelot, Marie-Elise; Michiels, Christelle; Schwartz, Sharon B; Bocquet, Béatrice; Antonio, Aline; Audier, Claire; Letexier, Mélanie; Saraiva, Jean-Paul; Luu, Tien D; Sennlaub, Florian; Nguyen, Hoan; Poch, Olivier; Dollfus, Hélène; Lecompte, Odile; Kohl, Susanne; Sahel, José-Alain; Bhattacharya, Shomi S; Audo, Isabelle


    Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG). The b-wave amplitude is severely reduced in the dark-adapted state of the ERG, representing abnormal function of ON bipolar cells. Furthermore, individuals with cCSNB can show other ocular features such as nystagmus, myopia, and strabismus and can have reduced visual acuity and abnormalities of the cone ERG waveform. The mode of inheritance of this form can be X-linked or autosomal recessive, and the dysfunction of four genes (NYX, GRM6, TRPM1, and GPR179) has been described so far. Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440(∗)]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384(∗)]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs(∗)59]) in the same gene. Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB. The exact role of this LRR protein in cCSNB remains to be elucidated.

  4. Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family

    NARCIS (Netherlands)

    Morava, E.; Kuhnisch, J.; Drijvers, J.M.; Robben, J.H.; Cremers, C.W.R.J.; Setten, P. van; Branten, A.J.W.; Stumpp, S.; Jong, A. de; Voesenek, K.E.J.; Vermeer, S.; Heister, A.; Claahsen-van der Grinten, H.L.; O'Neill, C.W.; Willemsen, M.H.; Lefeber, D.J.; Deen, P.M.T.; Kornak, U.; Kremer, J.M.J.; Wevers, R.A.


    CONTEXT: Mutations in ANKH cause the highly divergent conditions familial chondrocalcinosis and craniometaphyseal dysplasia. The gene product ANK is supposed to regulate tissue mineralization by transporting pyrophosphate to the extracellular space. OBJECTIVE: We evaluated several family members of

  5. Congenital sensorineural deafness in Australian stumpy-tail cattle dogs is an autosomal recessive trait that maps to CFA10.

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    Susan Sommerlad

    -value = 3.64, as was both coat colour and speckling. Fine mapping was then performed on 45 of these 50 dogs and a further 48 dogs (n = 93. Sequencing candidate gene Sox10 in 6 hearing ASCD, 2 unilaterally deaf ASCD and 2 bilaterally deaf ASCD did not reveal any disease-associated mutations. CONCLUSIONS: Deafness in ASCD is an incompletely penetrant autosomal recessive inherited disease that maps to CFA10.

  6. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

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    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  7. Skeletal muscle, but not cardiovascular function, is altered in a mouse model of autosomal recessive hypophosphatemic rickets

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    Michael J. Wacker


    Full Text Available Autosomal recessive hypophosphatemic rickets (ARHR is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL- fast-twitch muscle, soleus (SOL- slow-twitch muscle, heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2a or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In

  8. Hereditary palmoplantar keratosis of the Gamborg Nielsen type. Clinical and ultrastructural characteristics of a new type of autosomal recessive palmoplantar keratosis. (United States)

    Kastl, I; Anton-Lamprecht, I; Gamborg Nielsen, P


    A new kind of diffuse palmoplantar keratoderma with autosomal recessive inheritance and without associated symptoms was described in Norrbotten, Sweden by Gamborg Nielsen in 1985. Clinically, it ranges between the less severe dominant Unna-Thost type and the more severe recessive Meleda type, as it is milder than the latter. Skin biopsies of five patients from three different families with this new palmoplantar keratoderma, as well as five obligatory heterozygotes from one family, were investigated ultrastructurally in order to characterize this new entity and to differentiate it from the Meleda type. Several features are common to both autosomal recessive palmoplantar keratoses. They show a broadened granular layer, a transit region consisting of cells with a marginal envelope, and considerable hyperkeratosis. Morphologically, this transformation delay is less pronounced in the Gamborg Nielsen type than in the classical Meleda type. As is typical for ridged skin, both types of palmoplantar keratoses possess composite keratohyaline granules. In contrast to the normal appearance of keratohyaline granules in the Meleda type, the Gamborg Nielsen type also shows qualitative deviations of keratohyaline granules with different degrees of spongiosity and electron density and sometimes with a granular border. It seems that abnormal keratohyaline proteins are synthesized that behave differently. The sudden transformation of a granular into a horny cell is physiologically regulated by different enzymes. A delay in this process may be caused by a mutation that reduces or alters the enzymes concerned. We assume the palmoplantar keratoderma of the Gamborg Nielsen type to be a variant of the heterogeneous group of the Meleda type of palmoplantar keratoderma with autosomal recessive inheritance.

  9. The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

    DEFF Research Database (Denmark)

    Riess, O; Noerremoelle, A; Weber, B


    including 196 bp of the 5' region of the PDEB gene have been assessed for mutations by using single-strand conformational polymorphism analysis in 14 patients from 13 unrelated families with autosomal recessive retinitis pigmentosa (ARRP). No disease-causing mutations were found in this group of affected...... individuals of seven different ancestries. However, a frequent intronic and two exonic polymorphisms (Leu489----Gln and Gly842----Gly) were identified. Segregation analysis using these polymorphic sites excludes linkage of ARRP to the PDEB gene in a family with two affected children....

  10. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report. (United States)

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem


    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  11. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia

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    Zamba-Papanicolaou Eleni


    Full Text Available Abstract Background Senataxin (chromosome 9q34 was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA, termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2 and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP. Here, we report a novel Senataxin mutation in a Cypriot ARCA family. Methods We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA families for linkage to known ARCA gene loci. We linked one family (909 to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing. Results Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients. Conclusion We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.

  12. Whole-exome sequencing reveals a novel frameshift mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in the Indian population. (United States)

    Zhou, Yu; Saikia, Bibhuti B; Jiang, Zhilin; Zhu, Xiong; Liu, Yuqing; Huang, Lulin; Kim, Ramasamy; Yang, Yin; Qu, Chao; Hao, Fang; Gong, Bo; Tai, Zhengfu; Niu, Lihong; Yang, Zhenglin; Sundaresan, Periasamy; Zhu, Xianjun


    Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 50 genes. To identify genetic mutations underlying autosomal recessive RP (arRP), we performed whole-exome sequencing study on two consanguineous marriage Indian families (RP-252 and RP-182) and 100 sporadic RP patients. Here we reported novel mutation in FAM161A in RP-252 and RP-182 with two patients affected with RP in each family. The FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. By whole-exome sequencing we identified several homozygous genomic regions, one of which included the recently identified FAM161A gene mutated in RP28-linked arRP. Sequencing analysis revealed the presence of a novel homozygous frameshift mutation p.R592FsX2 in both patients of family RP-252 and family RP-182. In 100 sporadic Indian RP patients, this novel homozygous frameshift mutation p.R592FsX2 was identified in one sporadic patient ARRP-S-I-46 by whole-exome sequencing and validated by Sanger sequencing. Meanwhile, this homozygous frameshift mutation was absent in 1000 ethnicity-matched control samples screened by direct Sanger sequencing. In conclusion, we identified a novel homozygous frameshift mutations of RP28-linked RP gene FAM161A in Indian population.

  13. A Missense Mutation in the LIM2 Gene Is Associated with Autosomal Recessive Presenile Cataract in an Inbred Iraqi Jewish Family (United States)

    Pras, Eran; Levy-Nissenbaum, Etgar; Bakhan, Tangiz; Lahat, Hadas; Assia, Ehud; Geffen-Carmi, Noa; Frydman, Moshe; Goldman, Boleslaw; Pras, Elon


    In an inbred Iraqi Jewish family, we have studied three siblings with presenile cataract first noticed between the ages of 20 and 51 years and segregating in an autosomal recessive mode. Using microsatellite repeat markers in close proximity to 25 genes and loci previously associated with congenital cataracts in humans and mice, we identified five markers on chromosome 19q that cosegregated with the disease. Sequencing of LIM2, one of two candidate genes in this region, revealed a homozygous T→G change resulting in a phenylalanine-to-valine substitution at position 105 of the protein. To our knowledge, this constitutes the first report, in humans, of cataract formation associated with a mutation in LIM2. Studies of late-onset single-gene cataracts may provide insight into the pathogenesis of the more common age-related cataracts. PMID:11917274

  14. Novel homozygous mutations in the EVC and EVC2 genes in two consanguineous families segregating autosomal recessive Ellis-van Creveld syndrome. (United States)

    Aziz, Abdul; Raza, Syed I; Ali, Salman; Ahmad, Wasim


    Ellis-van Creveld syndrome (EVC) is a rare developmental disorder characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, teeth, oral and cardiac abnormalities. It is caused by biallelic mutations in the EVC or EVC2 gene, separated by 2.6 kb of genomic sequence on chromosome 4p16. In the present study, we have investigated two consanguineous families of Pakistani origin, segregating EVC in autosomal recessive manner. Linkage in the families was established to chromosome 4p16. Subsequently, sequence analysis identified a novel nonsense mutation (p.Trp234*) in exon 8 of the EVC2 gene and 15 bp duplication in exon 14 of the EVC gene in the two families. This further expands the mutations in the EVC or EVC2 genes resulting in the EVC syndrome.

  15. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism. (United States)

    Bowl, Michael R; Mirczuk, Samantha M; Grigorieva, Irina V; Piret, Sian E; Cranston, Treena; Southam, Lorraine; Allgrove, Jeremy; Bahl, Shailini; Brain, Caroline; Loughlin, John; Mughal, Zulf; Ryan, Fiona; Shaw, Nick; Thakker, Yogini V; Tiosano, Dov; Nesbit, M Andrew; Thakker, Rajesh V


    GCMB is a member of the small transcription factor family GCM (glial cells missing), which are important regulators of development, present in vertebrates and some invertebrates. In man, GCMB encodes a 506 amino acid parathyroid gland-specific protein, mutations of which have been reported to cause both autosomal dominant and autosomal recessive hypoparathyroidism. We ascertained 18 affected individuals from 12 families with autosomal recessive hypoparathyroidism and have investigated them for GCMB abnormalities. Four different homozygous germline mutations were identified in eight families that originate from the Indian Subcontinent. These consisted of a novel nonsense mutation R39X; a missense mutation, R47L in two families; a novel missense mutation, R110W; and a novel frameshifting deletion, I298fsX307 in four families. Haplotype analysis, using polymorphic microsatellites from chromosome 6p23-24, revealed that R47L and I298fsX307 mutations arose either as ancient founders, or recurrent de novo mutations. Functional studies including: subcellular localization studies, EMSAs and luciferase-reporter assays, were undertaken and these demonstrated that: the R39X mutant failed to localize to the nucleus; the R47L and R110W mutants both lost DNA-binding ability; and the I298fsX307 mutant had reduced transactivational ability. In order to gain further insights, we undertook 3D-modeling of the GCMB DNA-binding domain, which revealed that the R110 residue is likely important for the structural integrity of helix 2, which forms part of the GCMB/DNA binding interface. Thus, our results, which expand the spectrum of hypoparathyroidism-associated GCMB mutations, help elucidate the molecular mechanisms underlying DNA-binding and transactivation that are required for this parathyroid-specific transcription factor.

  16. Two cases of autosomal recessive generalized dystonia in childhood: 5 year follow-up and bilateral globus pallidus stimulation results

    NARCIS (Netherlands)

    Lenders, Mathieu W.; Vergouwen, Mervyn D.; Hageman, Gerard; Hoek, van der Joffrey A.; Ippel, Elly F.; Jansen Steur, Ernst N.; Buschman, Hendrik P.J.; Hariz, Marwan


    We report two brothers with an unknown form of early-onset familiar dystonia. Characteristic clinical features are (1) childhood-onset; (2) extrapyramidal motor symptoms; (3) dysarthria; and (4) mental retardation. Additional findings include loss of D2-receptors in both basal ganglia and hypoplasia

  17. Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa-associated locus, develop severe early-onset retinal degeneration. (United States)

    Kevany, Brian M; Zhang, Ning; Jastrzebska, Beata; Palczewski, Krzysztof


    Genetic mapping was recently used to identify the underlying cause for a previously uncharacterized cohort of autosomal recessive retinitis pigmentosa cases. Genetic mapping of affected individuals resulted in the identification of an uncharacterized gene, C2Orf71, as the causative locus. However, initial homology searches failed to reveal similarities to any previously characterized protein or domain. To address this issue, we characterized the mouse homolog, BC027072. Immunohistochemistry with a custom polyclonal antibody showed staining localized to the inner segments (IS) of photoreceptor cells, as well as the outer segments (OS) of cone cells. A knockout mouse line (BC(-/-)) was generated and demonstrated that loss of this gene results in a severe, early-onset retinal degeneration. Histology and electron microscopy (EM) revealed disorganized OS as early as 3 weeks with complete loss by 24 weeks of age. EM micrographs displayed packets of cellular material containing OS discs or IS organelles in the OS region and abnormal retinal pigmented epithelium cells. Analyses of retinoids and rhodopsin levels showed retinal degenerations. Although its function remains unknown, this protein appears essential for normal OS development/maintenance and vision in humans and mice. RNAseq data are available in the GEO database under accession: GSE63810.

  18. Clinical Application of Screening for GJB2 Mutations before Cochlear Implantation in a Heterogeneous Population with High Rate of Autosomal Recessive Nonsyndromic Hearing Loss

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    Masoud Motasaddi Zarandy


    Full Text Available Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs and speech recognition thresholds (SRTs improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all >0.10. Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, =0.22. Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.

  19. A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. (United States)

    Bicknell, Louise S; Pitt, James; Aftimos, Salim; Ramadas, Ram; Maw, Marion A; Robertson, Stephen P


    There are several rare syndromes combining wrinkled, redundant skin and neurological abnormalities. Although phenotypic overlap between conditions has suggested that some might be allelic to one another, the aetiology for many of them remains unknown. A consanguineous New Zealand Maori family has been characterised that segregates an autosomal recessive connective tissue disorder (joint dislocations, lax skin) associated with neurological abnormalities (severe global developmental delay, choreoathetosis) without metabolic abnormalities in four affected children. A genome-screen performed under a hypothesis of homozygosity by descent for an ancestral mutation, identified a locus at 10q23 (Z = 3.63). One gene within the candidate interval, ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), was considered a plausible disease gene since a missense mutation had previously been shown to cause progressive neurodegeneration, cataracts, skin laxity, joint dislocations and metabolic derangement in a consanguineous Algerian family. A missense mutation, 2350C>T, was identified in ALDH18A1, which predicts the substitution H784Y. H784 is invariant across all phyla and lies within a previously unrecognised, conserved C-terminal motif in P5CS. In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5CS was not affected by the H784Y substitution. These data suggest that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.

  20. SIPA1L3 identified by linkage analysis and whole-exome sequencing as a novel gene for autosomal recessive congenital cataract. (United States)

    Evers, Christina; Paramasivam, Nagarajan; Hinderhofer, Katrin; Fischer, Christine; Granzow, Martin; Schmidt-Bacher, Annette; Eils, Roland; Steinbeisser, Herbert; Schlesner, Matthias; Moog, Ute


    Congenital cataract (CC) is one of the most important causes for blindness or visual impairment in infancy. A substantial proportion of isolated CCs has monogenic causes. The disease is genetically heterogeneous, and all Mendelian modes of inheritance have been reported. We mapped a locus for isolated CC on 19p13.1-q13.2 in a distantly consanguineous German family with two sisters affected by dense white cataracts. Whole-exome sequencing identified a homozygous nonsense variant c.4489C>T (p.(R1497*)) in SIPA1L3 (signal-induced proliferation-associated 1 like 3) in both affected children. SIPA1L3 encodes a GTPase-activating protein (GAP), which interacts with small GTPases of the Rap family via its Rap-GAP-domain. The suggested role of Rap GTPases in cell growth, differentiation and organization of the cytoskeleton in the human lens, and lens-enriched expression of the murine ortholog gene Sipa1l3 in embryonic mice indicates that this gene is crucial for early lens development. Our results provide evidence that sequence variants in human SIPA1L3 cause autosomal recessive isolated CC and give new insight into the molecular pathogenesis underlying human cataracts.

  1. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness. (United States)

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine


    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium.

  2. Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis.

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    Doroteya Raykova

    Full Text Available Pure hair and nail ectodermal dysplasia (PHNED comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T>C variant (p.Phe274Ser in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/hypotrichosis simplex (ADWH. Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.

  3. An autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa maps to chromosome 17q24.2-25.3

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    Bouhouche Ahmed


    Full Text Available Abstract Background Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern. Methods All family members underwent neurological and radiological examinations. A genome wide search was conducted in this family using the ABI PRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate genes within the region linked to the disease were screened for mutations by direct sequencing. Results Evidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis of recombination events and LOD score calculation suggests linkage of the responsible gene in a genetic interval of 11 Mb located between D17S789 and D17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven candidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and GRIN2C, identified three missense mutations in the FDXR gene which were also found in a homozygous state in three healthy controls, suggesting that these variants are not disease-causing mutations in the family. Conclusion A novel locus for leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome 17q24.2-25.3 in a consanguineous Moroccan family.

  4. Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD). (United States)

    Gao, Ying; Erokwu, Bernadette O; DeSantis, David A; Croniger, Colleen M; Schur, Rebecca M; Lu, Lan; Mariappuram, Jose; Dell, Katherine M; Flask, Chris A


    Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1  = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R = 0.85, p = 0.002), periportal fibrosis area percent (R = 0.82, p = 0.004), and hydroxyproline content (R = 0.76, p = 0.01). These results suggest that hepatic T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease.

  5. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A


    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  6. Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

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    Cornel Martina C


    Full Text Available Abstract Background The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. Methods/Design This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. Discussion This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous

  7. MRI assessment of fetal autosomal recessive polycystic kidney disease%常染色体隐性遗传性多囊肾病胎儿的MRI表现

    Institute of Scientific and Technical Information of China (English)

    董素贞; 朱铭; 钟玉敏; 张弘; 潘慧红


    目的 探讨MRI对常染色体隐性遗传性多囊肾病(ARPKD)胎儿的诊断价值.方法 回顾性分析2005年7月至2013年12月间产前超声检查提示异常,然后行MR检查,并经引产后尸解或病理证实的ARPKD胎儿16例.MR扫描序列主要采用稳态自由进动(SSFP)序列、单次激发快速自旋回波(SSTSE)序列和快速加权序列T1WI.将产前MRI、超声表现与引产后尸解或病理结果进行对照分析.结果 16例ARPKD患儿均表现为双侧肾脏体积明显增大,SSTSE序列肾髓质弥漫性高信号小囊肿.11例合并羊水过少,11例合并双肺发育不良,6例合并肝纤维化.11例双肺发育不良和6例肝脏轻度纤维化超声均未提示,肾脏病变超声误诊1例,MRI诊断均正确.结论 MRI诊断胎儿ARPKD具有明显优势,不受羊水量的影响,能准确评价肾脏及肺异常.%Objective To explore the value of MRI on fetal autosomal recessive polycystic kidney disease (ARPKD).Methods Sixteen pregnant women,aged from 28 to 38 years (average 30 years) and with gestation age from 22 to 36 weeks (average 25 weeks) underwent MR scanning with a 1.5 T MR unit within 24 to 48 hours after ultrasound examinations.The imaging sequences included steady-state free-precession (SSFP) sequence,single-shot turbo spin echo (SSTSE) sequence and T1-weighted fast imaging sequence.Prenatal US and MR imaging findings were compared with autopsy or pathological results.Results A total of 16 cases of ARPKD showed bilateral markedly enlarged kidneys and diffuse high signal small cysts in renal medulla on SSTSE sequence.Among the 16 cases,11 cases were with oligohydramnios,1 1 cases were with pulmonary hypoplasia,and 6 cases were with hepatic fibrosis.Eleven cases of pulmonary hypoplasia and 6 cases of hepatic fibrosis were all missed by US.For the diagnosis of the renal anomalies,US missed one case.MRI diagnosis was correct in all these cases.Conclusions MRI shows great advantages on the diagnosis of fetal ARPKD

  8. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail:


    chlorophyllin on the damage caused by the radiation, it was into accothe presence of lethal and semi lethals autosomal. One observes this way that even without the use of the radiation the semi lethals frequency is diminished when the chlorophyllin is applied, in this case the decrease was significant and although there was decrease in the case of the irradiated group this it was not significant; in the case of the lethal ones it happened the opposite it was not significant in radiation absence on the contrary elevate the frequency of this type of genes, however, before the radiation and with pre-treatment with chlorophyllin this it reduced the frequency of autosomal recessive lethals significantly. This is important because in the case of bound recessive lethals recessive to the sex this doesn't happen. (Author)

  9. Uniparental disomy of chromosome 8 leading to homozygosity of a CYP11B1 mutation in a patient with congenital adrenal hyperplasia: implication for a rare etiology of an autosomal recessive disorder. (United States)

    Matsubara, Keiko; Kataoka, Naoki; Ogita, Satoko; Sano, Shinichiro; Ogata, Tsutomu; Fukami, Maki; Katsumata, Noriyuki


    Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that usually results from paternally and maternally transmitted mutations in genes for steroidogenic enzymes. Recent studies on steroid 21-hydroxylase deficiency, the most common form of CAH, have revealed that a small percentage of patients have a non-carrier parent; uniparental disomy (UPD) and de novo mutations were reported as disease-causing mechanisms in these patients. However, it remains unknown whether UPD and de novo mutations underlie other forms of CAH. Here, we report a male patient with steroid 11β-hydroxylase deficiency (11OHD) born to a non-carrier mother. The patient was identified by an elevated 17-hydroxyprogesterone level at a neonatal mass-screening test. His clinical features were comparable to those of previously reported patients with 11OHD. Direct sequencing of CYP11B1 identified a homozygous IVS7+1G>A mutation in the patient, which was not shared by his mother. Comparative genomic hybridization of the patient detected UPD of chromosome 8 [UPD(8)]. Microsatellite analysis indicated non-maternal origin of the UPD(8) and confirmed parentage of other chromosomes. This study shows for the first time that 11OHD can be caused by UPD in the presence of a non-carrier parent. Awareness of such rare cases should improve the accuracy of genetic counseling for families with CAH. Our data support the importance of UPD as an underlying mechanism of autosomal recessive disorders.

  10. A neonate with Coombs-negative hemolytic jaundice with spherocytes but normal erythrocyte indices: a rare case of autosomal-recessive hereditary spherocytosis due to alpha-spectrin deficiency. (United States)

    Yaish, H M; Christensen, R D; Agarwal, A


    The diagnosis of hereditary spherocytosis (HS) in a newborn infant is generally made on the basis of a positive family history, spherocytes on blood film and Coombs-negative hemolytic jaundice of variable severity with an elevated mean corpuscular hemoglobin concentration (MCHC) and a low mean corpuscular volume (MCV). In general, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) quantification of erythrocyte membrane proteins is not needed to make the clinical diagnosis of HS. However, we observed that a neonate with no family history of HS, but with abundant spherocytosis on repeated blood films, Coombs-negative hemolytic jaundice and normal MCHC and MCV measurements, where SDS-PAGE revealed alpha-spectrin deficiency, a rare autosomal-recessive variety of HS that generally has a severe clinical phenotype.

  11. 常染色体隐性遗传性成骨不全症的分子遗传学研究进展%Advances on molecular genetics of autosomal recessive osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    曹丽华; 张学


    成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.%Osteogenesis imperfecta (OI) , also known as brittle bone disease, is a genetic disorder of connective tissue caused by structural or functional abnormality of type I collagen. OI is characterized by multiple bone fractures. Affected individuals may also have macrocephaly, blue sclerae,hearing loss, dentinogene-sis imperfecta, and kyphoscoliosis. OI shows marked clinical variability and genetic heterogeneity, and both autosomal dominant and recessive forms exist. In this paper, we will review the recent progress in molecular genetics of the autosomal recessive OI.

  12. Rescue of the temperature-sensitive, autosomal-recessive mutation R298S in the sodium-bicarbonate cotransporter NBCe1-A characterized by a weakened dimer and abnormal aggregation (United States)

    Gill, Harindarpal S.; Choi, Kun-Young; Kammili, Lakshmi; Popratiloff, Anastas


    Background Band keratopathy, an ocular disease that is characterized by hypercalcemia and opaque bands across the cornea, has been associated with kidney disease. Type-II renal tubular acidosis (RTA), a condition in which the kidneys fail to recover bicarbonate (HCO3−) in the proximal tubule of the nephron, results in HCO3− wastage in the urine and low blood pH. The development of these diseases is associated with autosomal-recessive mutations in the Na+-coupled HCO3− cotransporter NBCe1-A located at the basolateral membranes of either cell type. Methods We provide insight into the devastating R298S mutation found in type-II RTA-afflicted individuals using confocal-microscopy imaging of fluorescently-tagged NBCe1-A and NBCe1-A-R298S molecules expressed in human corneal endothelial and proximal tubule cells and from in-depth biophysical studies of their cytoplasmic N-terminal domains (Nt and Nt-R298S), including Nt crystal structure, melting-temperature, and homodimer dissociation constant (KD) analyses. Results We illuminate and rescue trafficking defects of the R298S mutation of NBCe1-A. The KD for Nt monomer-dimer equilibrium is established. The KD for Nt-R298S is significantly higher, but immeasurable due to environmental factors (pH, temperature, concentration) that result in dimer instability leading to precipitation. The crystal structure of Nt-dimer shows that R298 is part of a putative substrate conduit and resides near the dimer interface held together by hydrogen-bond networks. Conclusions The R298S is a temperature-sensitive mutation in Nt that results in instability of the colloidal system leading to abnormal aggregation. General significance Our findings provide new perspectives to the aberrant mechanism of certain ocular pathologies and type-II RTA associated with the R298S mutation. PMID:25743102

  13. Aberrant expression pattern of a novel mutation in connexin 26 gene resulting in autosomal recessive deafness%连接蛋白基因一个新致聋突变体p.Y155X及功能分析

    Institute of Scientific and Technical Information of China (English)

    杨中纯; 肖自安; 谢鼎华; 夏昆


    Objective To report a novel deafness-causing mutation c. 465T→A, p. Y155X in connexin 26 (CX26) (also called gap junction protein β-2, GJB2 ), and perform functional analysis of the mutated protein p. Y155X in Hela cells to explore the underlying mechanism on deafness. Methods Mutations in CX26 gene of the proband in an autosomal recessive inherited deafness family were tested by direct DNA sequencing method. Mutant p. Y155X, which was found in the deafness family, and wild type CX26 (wtCX26), were directionally subcloned into the pEGFP-N1 plasmid to construct the recombinant fusion protein expression vector of CX26 p. Y155X-EGFP and wtCX26-EGFP, followed by transfecting into HeLa cells. The expression of the mutated and wild type proteins was analyzed using Western blot analysis. The intracellular localization of proteins and the formation of gap junction-like plaques at plasma membrane were observed under confocal microscope. Gap junction coupling was tested by calcein-AM dye transfer experiment. Results A novel nonsense mutation c. 465T→A, p. Y155X in the CX26 gene was found in the autosomal recessive deafness family. The molecular weight of protein p. Y155X was smaller than that of wtCX26 in transiently expressed HeLa cells. The mutated protein failed to reach the cell surface to form gap junction plaques, and displayed cytoplasmic accumulation. Also, no calcein-AM dye was transferred from the donor cells to the recipient cells when both were transfected with CX26 p. Y155X. The wtCX26 protein localized at the cell membrane to form gap junction plaques with permeability to fluorescent dye calcein-AM. Conclusion CX26 p. Y155X could not be targeted to the plasma membrane and there was no formation of gap junction channels between the adjacent cells. The mutation c. 465T→A, p. Y155X in CX26 gene was responsible for the autosomal recessive hearing impairment in this family.%目的 观察连接蛋白(connexin 26,CX26)基因的一个新致聋突变c.465T

  14. 常染色体隐性遗传多囊肾病 PKHD1基因检测%Detection of PKHD1 gene in autosomal recessive polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    宋红霞; 孙春梅; 韩蓁; 李媛; 周熙惠


    Objective To identify and analyze mutation in polycystic kidney and hepatic disease 1 ( PKHD1 ) in one abortion fetus of autosomal recessive polycystic kidney disease ( ARPKD).Methods Genome DNA was extracted from peripheral venous blood sampled from the fetus and his parents .PCR amplification and DNA direct sequencing and other technical means were adopted to perform gene mutation analysis of PKHD1.Results The following DNA sequence variations were found , ISV7+51G>T in intron 7, c.1587T>C(p. N529N) in exon 17, c.3785C>T(p.A1262V) in exon 32, which caused amino acid substitution from Alanine to Valine .Conclusion The variation of PKHD1 sequence may be involved in the pathogenesis of ARPKD .The sequence analysis of PKHD1 gene can be used as an effective method for prenatal diagnosis .%目的对1例引产的常染色体隐性遗传性多囊肾病胎儿的多囊肾/多囊肝病变1基因( PKHD1)进行基因突变鉴定和结果分析。方法采集引产胎儿及其父母外周静脉血,分别提取基因组DNA,应用PCR扩增、DNA直接测序等技术手段对该胎儿及其父母进行PKHD1基因突变分析。结果胎儿PKHD1基因出现几种序列变异:PKHD1基因第7号内含子发生ISV7+51G>T变异;第17号外显子发生c.1587T>C(p.N529N)变异;第32号外显子发生c.3785C>T(p.A1262V)变异,导致编码PKHD1蛋白多肽链第1262号氨基酸由丙氨酸变为缬氨酸。结论 PKHD1基因序列变异可能是常染色体隐性遗传性多囊肾病的病因,PKHD1基因检测可作为产前筛查的有效诊断手段。

  15. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

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    Woods C Geoffrey


    Full Text Available Abstract Background Cerebral palsy (CP is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67, involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA. Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS, epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts. Table 4 GAD1 single nucleotide substitutions detected on mutation analysis and occurring in sequences submitted to NCBI SNP database and in the literature. This is not a definitive list, but includes those described at the time of the mutational analysis. *Nucleotide positions were not provided by Maestrini et al. [47]. Source SNP position in mRNA, from the translational start site (bp Gene position of SNP(bp Amino acid change (ALappalainen et al. (2002 A(-478Del Exon

  16. Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism. (United States)

    Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos


    Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster wild type Canton-S acutely or chronically treated with paraquat (PQ), a selective toxin for elimination of dopaminergic (DAergic) neurons by oxidative stress (OS), as model of Parkinson's disease (PD). This study reports for the first time that knock-down (K-D) parkin Drosophila melanogaster (TH-GAL4; UAS-RNAi-parkin) chronically exposed to PQ (0.1-0.25 mM), FeSO(4) (Fe, 0.1mM), deferoxamine (DFO, 0.01 mM) alone or (0.1mM) PQ in combination with polyphenols propyl gallate (PG, 0.1mM) and epigallocathecin gallate (EGCG, 0.1, 0.5mM) showed significantly higher life span and locomotor activity than untreated K-D flies or treated with (1, 5, 20mM) PQ alone. Whilst gallic acid (GA, 0.1, 0.5mM) alone or in the presence of PQ provoked no effect on K-D flies, epicathecin (EC, 0.5mM) only showed a positive effect on prolonging K-D flies' life span. It is shown that PG (and EGCG) protected protocerebral posterolateral 1 (PPL1) DAergic neurons against PQ. Interestingly, the protective effect of low PQ concentrations, DFO and iron might be explained by a phenomenon known as "hormesis." However, pre-fed K-D flies with (0.1mM) PQ for 7 days and then exposed to (0.25 mM) for additional 8 days affect neither survival nor climbing of K-D Drosophila compared to flies treated with (0.25 mM) PQ alone. Remarkably, K-D flies treated with 0.1mM PQ (7 days) and then with (0.25 mM) PQ plus PG (8 days) behaved almost as flies treated with (0.25 mM) PQ. Taken these data suggest that antioxidant supplements that synergistically act with low pro-oxidant stimuli to prolong and increase locomotor activity become inefficient once a threshold of OS has been reached in K-D flies. Our present findings support the notion that genetically altered Drosophila melanogaster as suitable model to study genetic and environmental factors as causal and/or modulators in the development of autosomal

  17. Aspectos clínicos da doença renal policística autossômica recessiva DRPAR Clinical aspects of autosomal recessive polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Natasha Favoretto Dias


    Full Text Available INTRODUÇÃO: A Doença Renal Policística Autossômica Recessiva (DRPAR é uma causa importante de morbidade e mortalidade pediátricas, com um espectro variável de manifestações clínicas. MÉTODOS: A apresentação e evolução clínica de 25 pacientes (Pts foram analisadas através da revisão de prontuários, aplicando-se os formulários propostos por Guay-Woodford et al. As morbidades associadas à doença foram avaliadas quanto à frequência e à idade de manifestação. RESULTADOS: A idade média de diagnóstico foi de 61,45 meses (0 a 336,5 meses, com distribuição similar entre os sexos (52% dos pts do sexo feminino. Houve histórico familiar da doença em 20% dos casos (5/25, com dois casos de consanguinidade. Na análise inicial, diagnosticou-se hipertensão arterial (HAS em 56% dos Pts (14/25; doença renal crônica estágio > 2 (DRC > 2 em 24% (6/25; infecções do trato urinário (ITU em 40% (10/25 e hipertensão portal (HP em 32% dos casos (8/25. Das ultrassonografias abdominais iniciais, 80% demonstraram rins ecogênicos com cistos grosseiros e 64% detectaram fígado e vias biliares normais. Inibidores da ECA foram utilizados em 36% dos Pts, betabloqueadores em 20%, bloqueadores de canais de cálcio em 28% e diuréticos em 36% dos casos. Na análise final, após um tempo de acompanhamento médio de 152,2 meses (29,8 a 274,9 meses, HAS foi diagnosticada em 76% dos Pts, DRC > 2 em 44%, ITU em 52% e HP em 68%. CONCLUSÃO: As altas morbidade e mortalidade associadas à DRPAR justificam a construção de um banco de dados internacional, visando ao estabelecimento de um tratamento de suporte precoce.INTRODUCTION: Autosomal Recessive Polycystic Kidney Disease (ARPKD is an important pediatric cause of morbidity and mortality, with a variable clinical spectrum. METHODS: The clinical presentation and evolution of 25 patients (Pts were analyzed by clinical record review, according to the forms proposed by Guay-Woodford et al

  18. 三个常染色体隐性遗传早发型帕金森病家系的PARKIN基因研究%A study on PARKIN gene in three pedigrees with autosomal recessive early-onset Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    金淼; 焦劲松; 顾卫红; 王康; 邹海强; 陈彪; 王国相


    目的探讨PARKIN基因与中国人常染色体隐性遗传早发型帕金森病(autosomal recessive early-onset Parkinson's disease, AREP)家系的关系.方法对3个AREP家系的6例患者和23位成员进行系统的临床检查并进行PARKIN基因PCR扩增,产物通过变性高压液相色谱(denaturing high-performance liquid chromatography, DHPLC)进行突变检测,阳性结果标本进行基因测序.结果所有研究对象的PARKIN基因外显子均扩增成功.DHPLC检测和基因测序发现一个家系中存在PARKIN基因杂合Gly284Arg突变,另一个家系中存在PARKIN基因Ser167Asn多态性,且患者均有环境毒物接触史.结论 PARKIN基因杂合Gly284Arg突变在环境因素的协同作用下可能导致发病.PARKIN基因Ser167Asn多态性是帕金森病的易感因素,汞中毒与其共同作用可能导致发病.

  19. X-Linked and Autosomal Recessive Alport Syndrome

    DEFF Research Database (Denmark)

    Savige, Judith; Storey, Helen; Il Cheong, Hae


    Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all publishe...

  20. X-Linked and Autosomal Recessive Alport Syndrome

    DEFF Research Database (Denmark)

    Savige, Judith; Storey, Helen; Il Cheong, Hae;


    , retinopathy, lamellated glomerular basement membrane), variant pathogenicity was assessed using currently-accepted criteria, and variants were examined for gene location, and age at renal failure onset. Results were compared using Fisher's exact test (DNA Stata). Altogether 754 new DNA variants were...

  1. Autosomal recessive limb girdle myasthenia in two sisters.

    Directory of Open Access Journals (Sweden)

    Shankar A


    Full Text Available Limb girdle myasthenic syndromes are rare genetic disorders described under the broad heterogeneous group known as congenital myasthenic syndromes and present with mixed features of myasthenia and myopathy. The familial limb girdle myasthenia has been described as one with selective weakness of pectoral and pelvic girdles, showing a positive response to edrophonium chloride. A report of two sisters affected by this disorder is presented.

  2. Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance. (United States)

    Holme, S Alexander; Whatley, Sharon D; Roberts, Andrew G; Anstey, Alexander V; Elder, George H; Ead, Russell D; Stewart, M Felicity; Farr, Peter M; Lewis, Helen M; Davies, Nicholas; White, Marion I; Ackroyd, R Simon; Badminton, Michael N


    Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. We now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterized by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. No patient had evidence of liver dysfunction; four patients had neurological abnormalities. Patients were hetero- or homoallelic for nine different FECH mutations; four of which were previously unreported. Prokaryotic expression predicted that FECH activities were 2.7-25% (mean 10.6%) of normal. Neither mutation type nor FECH activity provided an explanation for the unusual phenotype. Our findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP that to our knowledge is previously unreported, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP.

  3. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia

    DEFF Research Database (Denmark)

    Hellström Pigg, Maritta; Bygum, Anette; Gånemo, Agneta;


    -100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27...

  4. Genetics Home Reference: autosomal recessive hyper-IgE syndrome (United States)

    ... attacks the body's own tissues and organs, causing autoimmune disease. For example, autoimmunity can lead to abnormal destruction of red blood cells (hemolytic anemia ) in people with AR-HIES. AR-HIES is ...

  5. 应用SYBR GreenⅠ实时荧光定量聚合酶链反应检测常染色体隐性遗传早发性帕金森综合征的parkin基因外显子重排突变%Analysis of exon rearrangements in the parkin gene in patients with autosomal recessive early-onset parkinsonism using SYBR Green Ⅰ Real-time PCR

    Institute of Scientific and Technical Information of China (English)

    唐北沙; 严新翔; 聂利珞; 郭纪锋; 张海南; 张学伟; 王磊; 沈璐; 江泓; 夏昆


    目的 建立应用SYBR GreenⅠ实时荧光定量聚合酶链反应(Real-time PCR,RT-PCR)检测parkin基因外显子重排突变的技术平台,应用该技术对常染色体隐性遗传早发型帕金森综合征(autosomal recessive early-onset parkinsonism,AREP) 家系进行parkin基因外显子重排突变分析.方法 应用SYBR GreenⅠRT-PCR技术对32个中国AREP家系进行parkin基因外显子重排突变分析.结果 14个家系先证者存在parkin基因外显子重排突变,其中3个为纯合缺失突变、3个为复杂杂合缺失突变和8个杂合缺失突变,未发现外显子重复突变,突变主要累及第2~4号外显子.结论 建立了应用SYBR GreenⅠRT-PCR技术检测parkin基因外显子重排突变的基因检测平台;中国AREP 家系的parkin基因外显子重排突变频率为43.8%,与国外报道相似.%Objective To develop a method of detection exon rearrangements in the parkin gene (PARK2) using SYBR Green Ⅰ real-time PCR and to analyze PARK2 exon rearrangement mutations in families with autosomal recessive early-onset parkinsonism (AREP) using this method. Methods Exon rearrangement in PARK2 was screened by SYBR Green Ⅰ real-time PCR in 32 families with AREP. Results Exon rearrangement mutations were found in 14 families, including 3 compound heterozygous deletions;3 homozygous deletions;and 8 heterozygous deletions. No duplication mutation was found. Hotspot for exon rearrangements clustered in exons 2 through 4. Conclusions We have developed a gene test method using SYBR Green Ⅰ Real-time PCR to detect exon rearrangements in the gene PARK2. The frequency of PARK2 mutation is 43.8% in Chinese families with AREP. This frequency is similar to reported findings in other countries.

  6. 常染色体隐性遗传的类Duchenne肌营养不良临床特征及其发生比率的估计值分析%The Proportion and Clinical Feature of Duchenne Muscular Dystrophy With Autosomal Recessive Inheritance

    Institute of Scientific and Technical Information of China (English)

    麻宏伟; 武盈玉; 王阳; 高薇; 薛燕宁


    目的:探讨常染色体隐性遗传的类杜氏肌营养不良(类DMD)临床特点及其在杜氏肌营养不良症(DMD)中的比例。方法:研究8个家系中9例女性类DMD的临床表现、家族史及血清肌酸激酶水平,并估计常染色体隐性遗传的类DMD在DMD中的比例。结果:常染色体隐性遗传的类DMD患者独立行走的平均时间为(1.47±1.00)岁,症状出现的平均时间为(8.11±4.32)岁,血清肌酸激酶平均水平为(2785.10±1500.29)U/L,这种常染色体隐性遗传型类DMD占DMD的9.4%。结论:常染色体隐性遗传的类DMD与DMD在临床上无法区别,部分被认为是性连锁隐性遗传的DMD,实际上是常染色体隐性遗传的类DMD。%Objective:Our aim was to investigate the proportion of autosomal recessive (AR) inheritance among families with patients with Duchenne muscular dystrophy (DMD) and clinical feature in patients with AR form of DMD. Methods:A total of 193 families was studied, 8 of them with at least one girl with “DMD - like” phenotype and 185 with only boys with this kind of phenotype. Based on the number of families with at least one affected girl and the number of patients per sibship among these pedigrees, the proportion of families with DMD inherited as an AR trait was estimated. The clinical examination, family history and serum creatine-kinase were studied in 11 patients diagnosed as AR form of DMD. Results: The proportion of families with AR form of DMD was estimated as 9.4%. The average age of being able to walk is (1.47±1.00) year, serum creatine-kinase levels were (2785.10±1500.29) U/L. The clinical symptom occurred at the average age of (8.11±4.32) year in patients with AR form of DMD. Conclusion: The AR form of muscular dystrophy and DMD not be distingushed clinically. Some families with only affected boys diagnosed as typical DMD, in fact, have the AR form of the disease. This study is very useful for genetic consulting.

  7. Exon rearrangement analysis of parkin gene in patients with autosomal recessive early-onset parkinsonism using fluorescent semi-quantitative PCR%应用荧光半定量聚合酶链反应方法检测常染色体隐性遗传早发性帕金森综合征parkin基因外显子重排突变分析

    Institute of Scientific and Technical Information of China (English)

    郭纪锋; 蔡芳; 潘乾; 沈璐; 江泓; 唐北沙; 夏昆; 严新翔; 张玉虎; 陈涛; 李静; 张学伟; 曹立


    目的探讨常染色体隐性遗传早发性帕金森综合征(autosomal recessive early-onset parkinsonism,AREP)parkin基因外显子重排突变情况.方法应用荧光半定量聚合酶链反应(PCR)方法对18个AREP家系进行parkin基因外显子重排突变分析.结果9个AREP家系含有parkin基因外显子重排突变,其中2个家系为外显子4纯合缺失,2个家系为外显子4杂合缺失,2个家系为外显子2杂合缺失,1家系为外显子3杂合缺失,1家系为外显子1杂合缺失,此外,1家系为外显子3和外显子4的复合杂合缺失.未见parkin基因外显子重复突变.结论我国AREP患者存在parkin基因外显子重排突变;parkin基因外显子重排突变可能是我国AREP患者的主要致病因素.

  8. CYBA突变所致儿童常染色体隐性遗传性慢性肉芽肿病二例临床特点和突变分析%Clinical features and molecular analysis of 2 Chinese children with autosomal recessive chronic granulomatous disease caused by CYBA mutations

    Institute of Scientific and Technical Information of China (English)

    贺建新; 赵顺英; 徐保平; 胡英惠; 申昆玲; 江载芳


    Objective To summarize clinical and molecular features of two children with autosomal recessive chronic granulomatous disease caused by CYBA mutations.Method The clinical records and CYBA mutations were reviewed for analysis of infections and inflammatory complications.Result The first case was a girl diagnosed with "liver and spleen abscess" in our hospital when she was 2.9 years old,with past history of neonatal impetigo and recurrent purulent lymphadenitis and positive family history.The results of DHR123 flow-cytometry showed that positive phagocytes after phorbol ester (PMA) stimulation was 84.63%.CYBA mutation analysis showed that she had heterozygous 35C > T,Q3X and IVS-2A > G.The second case was a boy diagnosed with" sepsis (salmonella D)" when he was 4 years old with a past history of impetigo,sepsis,perianal abscess,skin infection and positive family history.The results of flowcytometry showed that positive phagocytes after PMA stimulation was 96.13%.CYBA mutation analysis showed that he had homozygous 35C > T,Q3X and his parents were all carriers.All of them had BCG related axillary lymphnode calcification.Conclusion A22CGD cases had recurrent purulent infections (skin,lymphnode,liver and spleen,lung,blood),DHR123 flowcytometric analysis helped the diagnosis of CGD,CYBA mutation analysis ascertained the diagnosis of A22CGD.%目的 报道2例由细胞色素b,α亚单位(CYBA)突变所致常染色体隐性遗传性慢性肉芽肿病(A22CGD)患儿的临床表现及基因突变特点.方法 针对经DHR123流式细胞分析和CYBA基因突变分析明确诊断的2例A22CGD患儿,回顾其临床资料,总结与感染及炎症并发症相关的临床特点.结果 例1,女,2岁11个月,以肝脾脓肿入院,既往有新生儿脓疱疹,反复化脓性淋巴结炎病史.有2例同胞兄长生后早期高热夭折病史.DHR123流式细胞分析结果示佛波酯(PMA)刺激后阳性吞噬细胞为84.61%.CYBA基因突变分析为杂合的35T>C,Q3X

  9. Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. (United States)

    Higgins, Joseph J; Hao, Jin; Kosofsky, Barry E; Rajadhyaksha, Anjali M


    A nonsense mutation (R419X) in the human cereblon gene [mutation (mut) CRBN] causes a mild type of autosomal recessive nonsyndromal mental retardation (ARNSMR). CRBN, a cytosolic protein, regulates the assembly and neuronal surface expression of large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) in brain regions involved in memory and learning. Using the real-time quantitative polymerase chain reaction, we show that mut CRBN disturbs the development of adult brain BK(Ca) isoforms. These changes are predicted to result in BK(Ca) channels with a higher intracellular Ca(2+) sensitivity, faster activation, and slower deactivation kinetics. Such alterations may contribute to cognitive impairments in patients with mild ARNSMR.

  10. A mental retardation-linked nonsense mutation in cereblon is rescued by proteasome inhibition. (United States)

    Xu, Guoqiang; Jiang, Xiaogang; Jaffrey, Samie R


    A nonsense mutation in cereblon (CRBN) causes autosomal recessive nonsyndromic mental retardation. Cereblon is a substrate receptor for the Cullin-RING E3 ligase complex and couples the ubiquitin ligase to specific ubiquitination targets. The CRBN nonsense mutation (R419X) results in a protein lacking 24 amino acids at its C terminus. Although this mutation has been linked to mild mental retardation, the mechanism by which the mutation affects CRBN function is unknown. Here, we used biochemical and mass spectrometric approaches to explore the function of this mutant. We show that the protein retains its ability to assemble into a Cullin-RING E3 ligase complex and catalyzes the ubiquitination of CRBN-target proteins. However, we find that this mutant exhibits markedly increased levels of autoubiquitination and is more readily degraded by the proteasome than the wild type protein. We also show that the level of the mutant protein can be restored by a treatment of cells with a clinically utilized proteasome inhibitor, suggesting that this agent may be useful for the treatment of mental retardation associated with the CRBN R419X mutation. These data demonstrate that enhanced autoubiquitination and degradation account for the defect in CRBN activity that leads to mental retardation.

  11. "Dermatoglyphic Observations in an Iranian Girl Affected with Congenital Cutis Laxa (Autosomal Recessive"

    Directory of Open Access Journals (Sweden)

    H Pour-Jafari


    Full Text Available The aim of the this work was to determine the finger patterns, Finger Ridge Count (FRC, Total Finger Ridge Count (TFRC, and Asymmetry of Finger Ridge Count (AFRC of an Iranian girl (aged 13 years affected with congenital cutis laxa (CCL.The fingerprints of the first phalanx of both hands were taken by using the standard method (stamp ink. The fingerprints were classified according to the Galton nomenclature. The patterns of palm creases were also studied. Besides, the ridges of fingerprints of all ten fingers were counted, then employing the related formulas, the FRC, TFRC and AFRC were calculated.Results showed that the finger patterns of all ten fingers were radial loop; the major creases of the palms existed but their sizes were not normal. TFRC, which is the sum of all ten FRCs, was 77 (“low”, and AFRC was 10.344, more than that of her normal sister, that was 7.280. It is concluded that in CCL, the TFRC and symmetry of the fingertips ridges count may decrease; also palm pattern may be unusual.

  12. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet


    in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted...... in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal...

  13. Missense variants in AIMP1 gene are implicated in autosomal recessive intellectual disability without neurodegeneration

    NARCIS (Netherlands)

    Iqbal, Z.; Puttmann, L.; Musante, L.; Razzaq, A.; Zahoor, M.Y.; Hu, H; Wienker, T.F.; Garshasbi, M.; Fattahi, Z.; Gilissen, C.; Vissers, L.E.; Brouwer, A.P. de; Veltman, J.A.; Pfundt, R.P.; Najmabadi, H.; Ropers, H.H.; Riazuddin, S.; Kahrizi, K.; Bokhoven, H. van


    AIMP1/p43 is a multifunctional non-catalytic component of the multisynthetase complex. The complex consists of nine catalytic and three non-catalytic proteins, which catalyze the ligation of amino acids to their cognate tRNA isoacceptors for use in protein translation. To date, two allelic variants

  14. Genetic dissection of two Pakistani families with consanguineous localized autosomal recessive hypotrichosis (LAH

    Directory of Open Access Journals (Sweden)

    Seyyedha Abbas


    Conclusion:Both families were tested for linkage by genotyping polymorphic microsatellite markers linked to known alopecia loci. Family A excluded all known diseased regions that is suggestive of some novel chromosomal disorder. However, sequencing of P2RY5 gene in family B showed no pathogenic mutation.

  15. Autosomal recessive agammaglobulinemia: novel insights from mutations in Ig-beta. (United States)

    Lougaris, Vassilios; Ferrari, Simona; Cattalini, Marco; Soresina, Annarosa; Plebani, Alessandro


    Agammaglobulinemia is a rare primary immuno-deficiency characterized by an early block of B-cell development in the bone marrow resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. Mutations in the Bruton tyrosine kinase and in components of the pre-B-cell receptor (pre-BCR), such as mu heavy chain, surrogate light chain, and Igalpha have been found in 85% to 90% of patients affected by this disease. Here we review the recent advances in the characterization of molecular defects underlying an early block in B-cell development, focusing on the novel finding of the first two patients with agammaglobulinemia caused by mutations in Igbeta, the transmembrane protein that associates with Igalpha as part of the pre-BCR complex. Characterization of novel genetic defects involving components of the pre-BCR is crucial for a better understanding of the biology of early B-cell development and may have therapeutic and prognostic implications.

  16. Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain Anomalies, Cardiomyopathy, and Severe Intellectual Disability

    Directory of Open Access Journals (Sweden)

    R. Curtis Rogers


    Full Text Available Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome. Methods. Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients' descriptions are compared with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings. Results. The patients reported here include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies, gyral abnormalities, seizures, hypotonia, and cardiomyopathy. Conclusion. Vici syndrome should be suspected in any child with agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous hypopigmentation.

  17. Decreased bone density and treatment in patients with autosomal recessive cutis laxa.

    NARCIS (Netherlands)

    Noordam, C.; Funke, S.; Slobbe-Knoers, V.V.A.M.; Jira, P.E.; Wevers, R.A.; Urban, Z.; Morava, E.


    AIM: Due to the occasional association pathological fractures and osteoporosis we evaluated four patients with cutis laxa syndrome for skeletal anomalies. PATIENT/METHODS: We prospectively evaluated four patients, a male and a female child and a brother-sister sib pair, with dysmorphic features, gro

  18. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

    DEFF Research Database (Denmark)

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey


    , pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review...

  19. A homozygous missense mutation in the IRBP gene (RBP3) associated with autosomal recessive retinitis pigmentosa.

    NARCIS (Netherlands)

    Hollander, A.I. den; McGee, T.L.; Ziviello, C.; Banfi, S.; Dryja, T.P.; Gonzalez-Fernandez, F.; Ghosh, D.; Berson, E.L.


    PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP) has been considered essential for normal rod and cone function, as it mediates the transport of retinoids between the photoreceptors and the retinal pigment epithelium. This study was performed to determine whether mutations in the IRBP gen

  20. An autosomal recessive cerebellar ataxia syndrome with upward gaze palsy, neuropathy, and seizures

    NARCIS (Netherlands)

    Straussberg, R; Basel-Vanagaite, L; Kivity, S; Dabby, R; Cirak, S; Nurnberg, P; Voit, T; Mahajnah, M; Inbar, D; Saifi, GM; Lupski, [No Value; Delague, [No Value; Megarbane, A; Richter, A; Leshinsky, E; Berkovic, SF


    The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1, and SACS ge

  1. Identification of the CRB1 gene and analysis of its role in autosomal recessive retinal dystrophies

    NARCIS (Netherlands)

    Hollander, Antonia Ingrid den


    Inherited retinal dystrophies generally lead to severe visual impairment early in life. Most genes involved in retinal dystrophies are expressed exclusively or predominantly in the retina or the RPE. To identify candidate genes for inherited retinal dystrophies, we isolated

  2. [Autosomal recessive GTPCH 1 deficiency: the importance of the analysis of neurotransmitters in cerebrospinal fluid]. (United States)

    Moreno-Medinilla, E E; Mora-Ramirez, M D; Calvo-Medina, R; Martinez-Anton, J


    Introduccion. El deficit de la enzima trifosfato de guanosina ciclohidrolasa 1 (GTPCH 1) origina una disminucion de la sintesis de la tetrahidrobiopterina (BH4), cofactor indispensable en la sintesis de la tirosina, la dopamina y la serotonina. Es una enfermedad poco frecuente que produce un retraso o regresion psicomotora y trastornos del movimiento, y en la que el tratamiento puede mejorar o incluso corregir la clinica. Caso clinico. Niña afecta de deficit de GTPCH con herencia autosomica recesiva, diagnosticada a los 14 meses con estudio del liquido cefalorraquideo con deficit de pterinas, HVA y 5-HIAA, test de sobrecarga de fenilalanina y estudio genetico positivos. La clinica comenzo a los 5 meses con temblor cefalico y de las extremidades superiores, en reposo e intencional, intermitente, que desaparecio en un mes. El desarrollo psicomotor era normal, destacaba una hipotonia axial leve en la exploracion y las pruebas complementarias realizadas fueron normales. Posteriormente presento regresion psicomotora con perdida del sosten cefalico, disminucion de los movimientos activos, dificultad para la manipulacion bimanual, hipomimia e hipotonia global grave, lo que motivo el estudio de una encefalopatia progresiva. Tras el diagnostico de deficit de GTPCH, inicio tratamiento sustitutivo con levodopa/carbidopa, OH triptofano y BH4, con muy buena evolucion tanto motora como cognitiva. Actualmente, la paciente tiene 5 años, presenta un desarrollo psicomotor adecuado a su edad, cursa tercer curso de educacion infantil y ha alcanzado el nivel de su clase. Conclusion. Hay que destacar en este caso la mejoria tan satisfactoria, tanto motora como cognitiva, tras iniciar el tratamiento sustitutivo, ya que el nivel cognitivo suele quedar afectado en muchos casos.

  3. A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment

    NARCIS (Netherlands)

    Schrauwen, I.; Helfmann, S.; Inagaki, A.; Predoehl, F.; Tabatabaiefar, M.A.; Picher, M.M.; Sommen, M.; Seco, C.Z.; Oostrik, J.; Kremer, J.M.J.; Dheedene, A.; Claes, C.; Fransen, E.; Chaleshtori, M.H.; Coucke, P.; Lee, A.; Moser, T.; Camp, G. van


    CaBPs are a family of Ca(2+)-binding proteins related to calmodulin and are localized in the brain and sensory organs, including the retina and cochlea. Although their physiological roles are not yet fully elucidated, CaBPs modulate Ca(2+) signaling through effectors such as voltage-gated Ca(v) Ca(2

  4. CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria

    DEFF Research Database (Denmark)

    Saunders, Carol; Smith, Laurie; Wibrand, Flemming;


    of type IV 3-MGA-uria characterized by cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, and death in early childhood. Four of the individuals were of Greenlandic descent, and one was North American, of Northern European and Asian descent......3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific finding associated with mitochondrial dysfunction, including defects of oxidative phosphorylation. 3-MGA-uria is classified into five groups, of which one, type IV, is genetically heterogeneous. Here we report five children with a form...

  5. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta. (United States)

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C


    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  6. Screening for homozygosity by descent in families with autosomal recessive retinitis pigmentosa

    Indian Academy of Sciences (India)

    Kota Lalitha; Subhadra Jalali; Tejas Kadakia; Chitra Kannabiran


    Retinitis pigmentosa (RP) is a genetically heterogeneous disease and an important cause of blindness in the state of Andhra Pradesh in India. In an attempt to identify the disease locus in families with the recessive form of the disease, we used the approach of screening for homozygosity by descent in offspring of consanguineous and nonconsanguineous families with RP. Microsatellite markers closely flanking 21 known candidate genes for RP were genotyped in parents and affected offspring to determine whether there was homozygosity at these loci that was shared by affected individuals of a family. This screening approach may be a rapid preliminary method to test known loci for possible cosegregation with disease.


    Directory of Open Access Journals (Sweden)

    Jasmina IVANOVSKA


    Full Text Available PKU is the rare single-gene disease belonging to disturbance of metabolism of the amino acids, which in its own basics halved the mutated gene, whose leaning at the 12-chromosome charge for the synthesis of phenylalanine hydroxylase, turning on phenylalanine into tyrosine. Enzyme block usually leads to the accumulation of a toxic substrate and/or the deficient synthesis of a product needed for normal body function. In PKU there is a toxic accumulation of phenylalanine behind the deficient enzyme, phenylalanine hydrоxylase. The symptoms are: lighten hare, blue eyes, lithe pigmented skin, convulsion, mental retardation, low level of adrenalin caused for the lack of tyrosine, the urine have a specific smell of rats or gab.Inheritance of disease become in autosomal recessive way which always become possibility to stay hidden in the family and to inherit from knee to knee without manifestation of its own phenotype.The only therapy that successfully avoids the causes of this disease is phenylalanine-restricted diet. Today we have some affords for improvement of gene therapy, which can help us for determination to these disease. The success of the therapy depends from timing of the right detection also diagnostics all trough equivalent therapy which can successfully interrupt the new forms of mental retardation and other symptoms.

  8. Protein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity

    KAUST Repository

    Al-Tawashi, Azza


    Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been linked to severe autosomal recessive nonsyndromic mental retardation. Using a mouse model that produces a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show that CC2D1A is important for neuronal differentiation and brain development. CC2D1A mutant neurons are hypersensitive to stress and have a reduced capacitytoformdendritesandsynapsesinculture. Atthebiochemical level,CC2D1Atransduces signals to the cyclic adenosine 3?,5?-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell differentiation. PKA activity is compromised, and the translocation of its catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. Consistently, phosphorylation of the PKA target cAMP-responsive element-binding protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA complex to the membrane to facilitate signal transduction. Together, our data show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, which may be the underlying cause for impaired mental function in nonsyndromic mental retardation patients with CC2D1A mutation. 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31. (United States)

    Wali, A; John, P; Gul, A; Lee, K; Chishti, M S; Ali, G; Hassan, M J; Leal, S M; Ahmad, W


    Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2.

  10. Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23. (United States)

    Mowat, D R; Croaker, G D; Cass, D T; Kerr, B A; Chaitow, J; Adès, L C; Chia, N L; Wilson, M J


    We have identified six children with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short stature, four of whom presented with Hirschsprung (HSCR) disease in the neonatal period. HSCR was diagnosed in a further child at the age of 3 years after investigation for severe chronic constipation and another child, identified as sharing the same facial phenotype, had chronic constipation, but did not have HSCR. One of our patients has an interstitial deletion of chromosome 2, del(2)(q21q23). These children strongly resemble the patient reported by Lurie et al with HSCR and dysmorphic features associated with del(2)(q22q23). All patients have been isolated cases, suggesting a contiguous gene syndrome or a dominant single gene disorder involving a locus for HSCR located at 2q22-q23. Review of published reports suggests that there is significant phenotypic and genetic heterogeneity within the group of patients with HSCR, MR, and microcephaly. In particular, our patients appear to have a separate disorder from Goldberg-Shprintzen syndrome, for which autosomal recessive inheritance has been proposed because of sib recurrence and consanguinity in some families.

  11. Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability

    DEFF Research Database (Denmark)

    Hansen, Lars; Tawamie, Hasan; Murakami, Yoshiko


    PGAP2 encodes a protein involved in remodeling the glycosylphosphatidylinositol (GPI) anchor in the Golgi apparatus. After synthesis in the endoplasmic reticulum (ER), GPI anchors are transferred to the proteins and are remodeled while transported through the Golgi to the cell membrane. Germline...... rescue when we used strong promoters before the mutant cDNAs, suggesting a hypomorphic effect of the mutations. We report on alterations in the Golgi-located part of the GPI-anchor-biosynthesis pathway and extend the phenotypic spectrum of the GPI-anchor deficiencies to isolated intellectual disability...

  12. A novel mutation in the sterol 27-hydroxylase gene of a woman with autosomal recessive cerebrotendinous xanthomatosis

    Directory of Open Access Journals (Sweden)

    Garuti Rita


    Full Text Available Article abstract Mutations of the gene encoding the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1 gene cause defects in the cholesterol pathway to bile acids that lead to the storage of cholestanol and cholesterol in tendons, lenses and the central nervous system. This disorder is the cause of a clinical syndrome known as cerebrotendinous xanthomatosis (CTX. Since 1991 several mutations of the CYP27A1 gene have been reported. We diagnosed the clinical features of CTX in a caucasian woman. Serum levels of cholestanol and 7α-hydroxycholesterol were elevated and the concentration of 27-hydroxycholesterol was reduced. Bile alcohols in the urine and faeces were increased. The analysis of the CYP27A1 gene showed that the patient was a compound heterozygote carrying two mutations both located in exon 8. One mutation is a novel four nucleotide deletion (c.1330-1333delTTCC that results in a frameshift and the occurrence of a premature stop codon leading to the formation of a truncated protein of 448 amino acids. The other mutation, previously reported, is a C - > T transition (c. c.1381C > T that converts the glutamine codon at position 461 into a termination codon (p.Q461X. These truncated proteins are expected to have no biological function being devoid of the cysteine residue at position 476 of the normal enzyme that is crucial for heme binding and enzyme activity.

  13. Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations

    NARCIS (Netherlands)

    Avila-Fernandez, A.; Perez-Carro, R.; Corton, M.; Lopez-Molina, M.I.; Campello, L.; Garanto, A.; Fernandez-Sanchez, L.; Duijkers, L.; Lopez-Martinez, M.A.; Riveiro-Alvarez, R.; Silva, L.R. Da; Sanchez-Alcudia, R.; Martin-Garrido, E.; Reyes, N.; Garcia-Garcia, F.; Dopazo, J.; Garcia-Sandoval, B.; Collin, R.W.J.; Cuenca, N.; Ayuso, C.


    Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype-phenotype correlations. In a Spanish family with

  14. Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta (United States)

    Parry, David A.; Mighell, Alan J.; El-Sayed, Walid; Shore, Roger C.; Jalili, Ismail K.; Dollfus, Hélène; Bloch-Zupan, Agnes; Carlos, Roman; Carr, Ian M.; Downey, Louise M.; Blain, Katharine M.; Mansfield, David C.; Shahrabi, Mehdi; Heidari, Mansour; Aref, Parissa; Abbasi, Mohsen; Michaelides, Michel; Moore, Anthony T.; Kirkham, Jennifer; Inglehearn, Chris F.


    The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization. PMID:19200525

  15. A Novel Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohidrotic Ectodermal Dysplasia

    DEFF Research Database (Denmark)

    Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, D. L.;


    nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin...

  16. X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations. (United States)

    Savige, Judith; Storey, Helen; Il Cheong, Hae; Gyung Kang, Hee; Park, Eujin; Hilbert, Pascale; Persikov, Anton; Torres-Fernandez, Carmen; Ars, Elisabet; Torra, Roser; Hertz, Jens Michael; Thomassen, Mads; Shagam, Lev; Wang, Dongmao; Wang, Yanyan; Flinter, Frances; Nagel, Mato


    Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all published COL4A5, COL4A3 and COL4A4 variants in the LOVD databases. It also determined genotype-phenotype correlations for variants where clinical data were available. Individuals were referred for genetic testing where Alport syndrome was suspected clinically or on biopsy (renal failure, hearing loss, retinopathy, lamellated glomerular basement membrane), variant pathogenicity was assessed using currently-accepted criteria, and variants were examined for gene location, and age at renal failure onset. Results were compared using Fisher's exact test (DNA Stata). Altogether 754 new DNA variants were identified, an increase of 25%, predominantly in people of European background. Of the 1168 COL4A5 variants, 504 (43%) were missense mutations, 273 (23%) splicing variants, 73 (6%) nonsense mutations, 169 (14%) short deletions and 76 (7%) complex or large deletions. Only 135 of the 432 Gly residues in the collagenous sequence were substituted (31%), which means that fewer than 10% of all possible variants have been identified. Both missense and nonsense mutations in COL4A5 were not randomly distributed but more common at the 70 CpG sequences (pAla substitutions were underrepresented in all three genes (p< 0.0001) probably because of an association with a milder phenotype. The average age at end-stage renal failure was the same for all mutations in COL4A5 (24.4 ±7.8 years), COL4A3 (23.3 ± 9.3) and COL4A4 (25.4 ± 10.3) (COL4A5 and COL4A3, p = 0.45; COL4A5 and COL4A4, p = 0.55; COL4A3 and COL4A4, p = 0.41). For COL4A5, renal failure occurred sooner with non-missense than missense variants (p<0.01). For the COL4A3 and COL4A4 genes, age at renal failure occurred sooner with two non-missense variants (p = 0.08, and p = 0.01 respectively). Thus DNA variant characteristics that predict age at renal failure appeared to be the same for all three Alport genes. Founder mutations (with the pathogenic variant in at least 5 apparently- unrelated individuals) were not necessarily associated with a milder phenotype. This study illustrates the benefits when routine diagnostic laboratories share and analyse their data.

  17. High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sarika Kapoor


    Full Text Available Background/Aims: The PCK rat model of polycystic kidney disease is characterized by the progressive development of renal medullary cysts. Here, we evaluated the suitability of high resolution ultrasonography (HRU to assess the kidney and cyst volume in PCK rats, testing three different ultrasound image analysis methods, and correlating them with kidneys weights and histological examinations. Methods: After inducing anesthesia, PCK rats (n=18 were subjected to HRU to visualize the kidneys, to perform numeric and volumetric measurements of the kidney and any cysts observed, and to generate 3-dimensional images of the cysts within the kidney parenchyma. Results: HRU provided superior information in comparison to microscopic analysis of stained kidney sections. HRU-based kidney volumes correlated strongly with kidney weights (R2=0.809; PConclusion: HRU represents a useful diagnostic tool for kidney and cyst volume measurements in PCK rats. Sequential HRU examinations may be useful to study the effect of drugs on cyst growth without the need to euthanize experimental animals.

  18. Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance



    We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggest...

  19. Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia

    DEFF Research Database (Denmark)

    Grau, Tanja; Artemyev, Nikolai O; Rosenberg, Thomas


    characterization of six missense mutations applying the baculovirus system to express recombinant mutant and wildtype chimeric PDE6C/PDE5 proteins in Sf9 insect cells. Purified proteins were analyzed using Western blotting, phosphodiesterase (PDE) activity measurements as well as inhibition assays by zaprinast...

  20. New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish

    DEFF Research Database (Denmark)

    Morris-Rosendahl, Deborah J; Segel, Reeval; Born, A Peter


    Warburg Micro Syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. We have found...

  1. Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome

    NARCIS (Netherlands)

    Abou-Zahr, F; Bejjani, B; Kruyt, FAE; Kurg, R; Bacino, C; Shapira, SK; Youssoufian, H


    Seckel syndrome is a rare autosomal recessive disorder. The classical presentation includes pre- and postnatal growth deficiency, mental retardation, and characteristic facial appearance. There have been several reports of associated hematological abnormalities and chromosomal breakage, findings sug

  2. Children's Mental Health Surveillance (United States)

    Children’s Mental Health Surveillance What are childhood mental disorders? The term childhood mental disorder means all mental disorders that can ... is the impact of mental disorders in children? Mental health is important to overall health. Mental disorders are ...

  3. Mental Health (United States)

    Mental health includes our emotional, psychological, and social well-being. It affects how we think, feel and act as ... stress, relate to others, and make choices. Mental health is important at every stage of life, from ...

  4. Mental Disorders (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  5. Mental Health (United States)

    ... Viral Suppression Doctor, Clinical & Dental Visits Treatment Adherence Mental Health Substance Abuse Issues Sexual Health Nutrition & Food Safety Exercise Immunizations Aging with HIV/AIDS Women’s Health Housing ...

  6. Mental effort

    NARCIS (Netherlands)

    Kirschner, Paul A.; Kirschner, Femke


    Kirschner, P. A., & Kirschner, F. (2012). Mental effort. In N. Seel (Ed.), Encyclopedia of the sciences of learning, Volume 5 (pp. 2182-2184). New York, NY: Springer. doi:10.1007/978-1-4419-1428-6_226

  7. Good Mental Health (United States)

    ... Trying to conceive, pregnancy, and mental health Menstruation, menopause, and mental health Women veterans and mental health When you need help Good mental ... in Spanish ( en español ) Good mental health Nutrition and mental health Exercise and mental health Sleep ...

  8. Mental Byomdannelse

    DEFF Research Database (Denmark)

    Olsen, Tina Vestermann; Boye, Anne Mette; Borchmann, Inger Haarup;

    Formålet med publikationen er at præsentere metoden "Mental byomdannelse". Metoden viser, hvordan man via midlertidig brug af grunde kan undersøge et steds potentialer, tage et område i brug tidligt i en byomdannelsesproces og derved bidrage til at opbygge en ny identitet for området. Mental...... byomdannelse går ud på at skabe bevidsthed om et byudviklingsområde overfor byens borgere, kommende beboere og fremtidige brugere af området allerede mens den fysiske omdannelse er i gang. I publikationen præsenteres en værktøjskasse, som giver redskaber og ideer til, hvordan man kan sætte en mental...... byomdannelsesproces i gang i byens rum. Publikationen udgør en afrapportering fra et støttet forsøgsprojekt hvor metoden ”Mental byomdannelse” er udviklet ved at afprøve ideerne om mental byomdannelse i to cases i Ålborg Kommune, hhv. i Østre Havn og Nibe by. Formålet med at anvende metoden i de to cases har været...

  9. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease

    DEFF Research Database (Denmark)

    Gal, Andreas; Rau, Isabella; El Matri, Leila


    amino acid long secreted trypsin-like serine peptidase. The c.1066dupC is likely to result in a functional null allele, whereas the two point mutations predict the replacement of evolutionary conserved and functionally important residues. Molecular modeling of the p.Trp309Ser mutant suggests that both...... refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in two large Faroese families. We detected three different mutations in PRSS56. Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526......C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in five patients with arMCOP from a consanguineous Tunisian family. In one patient with MCOP from the Faroe Islands and in another one from Turkey, no PRSS56 mutation was detected, suggesting nonallelic...

  10. GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness

    NARCIS (Netherlands)

    N.S. Peachey (Neal ); T.A. Ray (Thomas A.); R.J. Florijn (Ralph); L.B. Rowe (Lucy ); T. Sjoerdsma (Trijntje); S. Contreras-Alcantara (Susana); K. Baba (Kenkichi); G. Tosini (Gianluca); N. Pozdeyev (Nikita); P.M. Iuvone (P. Michael); P. Bojang Jr. (Pasano); J.N. Pearring (Jillian ); H.J. Simonsz (Huib); M.M. van Genderen (Maria); D.G. Birch (David ); E.I. Traboulsi (Elias); A. Dorfman (Allison); I. Lopez (Irma); H. Ren (Huanan); A.F.X. Goldberg (Andrew ); P.M. Nishina (Patsy); P. Lachapelle (Pierre); M.A. McCall (Maureen ); R.K. Koenekoop (Robert); A.A.B. Bergen (Arthur); M. Kamermans; R.G. Gregg (Ronald)


    textabstractComplete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual f

  11. Autosomal Recessive Hereditary Agammaglobulinemia%常染色体隐性遗传的无丙种球蛋白血症

    Institute of Scientific and Technical Information of China (English)




  12. Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin

    DEFF Research Database (Denmark)

    Huppke, Peter; Brendel, Cornelia; Kalscheuer, Vera


    , hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous...

  13. ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA

    Directory of Open Access Journals (Sweden)

    D. Bahena-Bahena


    Full Text Available Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle proton pump. The ARCL-IIA syndrome characteristically presents a combined glycosylation defect affecting N-linked and O-linked glycosylations, differentiating it from other cutis laxa syndromes and classifying it as a Congenital Disorder of Glycosylation (ATP6V0A2-CDG. We studied two Mexican Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome. Both patients presented abnormal transferrin (N-linked glycosylation but Patient 1 had a normal ApoCIII (O-linked glycosylation profile. Mutational screening of ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported homozygous nonsense mutation c.187C>T (p.R63X associated with a novel clinical finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X mutation that had been previously reported but found that it also altered RNA processing generating a novel transcript not previously identified (r.2176_2293del; p.F726Sfs*10. This is the first report to describe Mestizo patients with molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their mutations are the first to be found in patients from different regions of the world and with different genetic backgrounds.

  14. Mutations in DCPS and EDC3 in autosomal recessive intellectual disability indicate a crucial role for mRNA decapping in neurodevelopment. (United States)

    Ahmed, Iltaf; Buchert, Rebecca; Zhou, Mi; Jiao, Xinfu; Mittal, Kirti; Sheikh, Taimoor I; Scheller, Ute; Vasli, Nasim; Rafiq, Muhammad Arshad; Brohi, M Qasim; Mikhailov, Anna; Ayaz, Muhammad; Bhatti, Attya; Sticht, Heinrich; Nasr, Tanveer; Carter, Melissa T; Uebe, Steffen; Reis, André; Ayub, Muhammad; John, Peter; Kiledjian, Megerditch; Vincent, John B; Jamra, Rami Abou


    There are two known mRNA degradation pathways, 3' to 5' and 5' to 3'. We identified likely pathogenic variants in two genes involved in these two pathways in individuals with intellectual disability. In a large family with multiple branches, we identified biallelic variants in DCPS in three affected individuals; a splice site variant (c.636+1G>A) that results in an in-frame insertion of 45 nucleotides and a missense variant (c.947C>T; p.Thr316Met). DCPS decaps the cap structure generated by 3' to 5' exonucleolytic degradation of mRNA. In vitro decapping assays showed an ablation of decapping function for both variants in DCPS. In another family, we identified a homozygous mutation (c.161T>C; p.Phe54Ser) in EDC3 in two affected children. EDC3 stimulates DCP2, which decaps mRNAs at the beginning of the 5' to 3' degradation pathway. In vitro decapping assays showed that altered EDC3 is unable to enhance DCP2 decapping at low concentrations and even inhibits DCP2 decapping at high concentration. We show that individuals with biallelic mutations in these genes of seemingly central functions are viable and that these possibly lead to impairment of neurological functions linking mRNA decapping to normal cognition. Our results further affirm an emerging theme linking aberrant mRNA metabolism to neurological defects.

  15. Identification of a novel homozygous mutation, TMPRSS3: c.535G>A, in a Tibetan family with autosomal recessive non-syndromic hearing loss.

    Directory of Open Access Journals (Sweden)

    Dongyan Fan

    Full Text Available Different ethnic groups have distinct mutation spectrums associated with inheritable deafness. In order to identify the mutations responsible for congenital hearing loss in the Tibetan population, mutation screening for 98 deafness-related genes by microarray and massively parallel sequencing of captured target exons was conducted in one Tibetan family with familiar hearing loss. A homozygous mutation, TMPRSS3: c.535G>A, was identified in two affected brothers. Both parents are heterozygotes and an unaffected sister carries wild type alleles. The same mutation was not detected in 101 control Tibetan individuals. This missense mutation results in an amino acid change (p.Ala179Thr at a highly conserved site in the scavenger receptor cysteine rich (SRCR domain of the TMPRSS3 protein, which is essential for protein-protein interactions. Thus, this mutation likely affects the interactions of this transmembrane protein with extracellular molecules. According to our bioinformatic analyses, the TMPRSS3: c.535G>A mutation might damage protein function and lead to hearing loss. These data suggest that the homozygous mutation TMPRSS3: c.535G>A causes prelingual hearing loss in this Tibetan family. This is the first TMPRSS3 mutation found in the Chinese Tibetan population.

  16. Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib? (United States)

    Fernández-Rebollo, Eduardo; Pérez de Nanclares, Guiomar; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald


    Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation.

  17. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis. (United States)

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B


    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

  18. Teen Mental Health (United States)

    ... worthless could be warning signs of a mental health problem. Mental health problems are real, painful, and sometimes severe. You ... things that could harm you or others Mental health problems can be treated. To find help, talk ...

  19. Mental Labels and Tattoos (United States)

    Hyatt, I. Ralph


    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  20. Disease: H00803 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00803 Seizures-sensorineural deafness-ataxia-mental retardation-electrolyte imbalance... (SESAME) ; SeSAME/EAST syndrome Seizures-sensorineural deafness-ataxia-mental retardation-electrolyte imbalance...deficit, and electrolyte imbalance. This disease links to autosomal recessive mut

  1. e mental

    Directory of Open Access Journals (Sweden)

    Luciana Maria Viviani


    Full Text Available This article deals with the history of Educational Biology (1933-1970 taking into account the development of this discipline in the Normal Schools in São Paulo (Brazil. The investigation is based on several kinds of documents, mainly teaching plans, programs, schoolbooks and testimonies from former teachers. It considers the projects for schools renovation developed since the 1920’s, as they produced certain kind of needs for the teacher education. It examines three periods of that history: the insertion of the discipline in the curriculum, its stability and decline. The focus is on the organization of the school subjects built by the pair heritage-environment. The conclusion is that the organization of this Educational Biology was based in the idea that the educators should act in a double productive way: in one side, to direct the students for the best physical and mental efficiency; in the other, to build ideal outlines for shape the children, women and teachers’s social behavior.

  2. Childhood encephalomyopathy with cytochrome c oxidase deficiency, ataxia, muscle wasting, and mental impairment. (United States)

    Angelini, C; Bresolin, N; Pegolo, G; Bet, L; Rinaldo, P; Trevisan, C; Vergani, L


    The son of third cousins was normal until age 2 when he had difficulty walking. At age 8 there was limb weakness, ataxia, loss of tendon reflexes, dislalia, and he was mildly retarded. During fasting, urinary organic acid excretion was abnormally high. Cytochrome c oxidase activity in muscle was 7% of the normal mean. The enzyme in platelets was 16% of controls with a decreased cytochrome aa3 peak. These data suggest an autosomal recessive transmission of this variant of cytochrome c oxidase deficiency.

  3. Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

    Directory of Open Access Journals (Sweden)

    Chograni Manèl


    Full Text Available Abstract Background To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC, mental retardation (MR and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families. Methods We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes PAX6, PITX3 and HSF4 are expressed in human brain and one gene LIM2 encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Results We report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly are reported. We detected three intronic variations in PAX6 gene: IVS4 -274insG (intron 4, IVS12 -174G>A (intron12 in the four studied families and IVS4 -195G>A (intron 4 in two families. Two substitutions polymorphisms in PITX3 gene: c.439 C>T (exon 3 and c.930 C>A (exon4 in one family. One intronic variation in HSF4 gene: IVS7 +93C>T (intron 7 identified in one family. And three intronic substitutions in LIM2 gene identified in all four studied families: IVS2 -24A>G (intron 2, IVS4 +32C>T (intron 4 and c.*15A>C (3'-downstream sequence. Conclusion Although the role of the four studied genes: PAX6, PITX3, HSF4 and LIM2 in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.

  4. Positive mental health and mental illness. (United States)

    Gilmour, Heather


    Based on the Mental Health Continuum Short Form administered in the 2012 Canadian Community Health Survey - Mental Health (CCHS-MH), the percentages of Canadians aged 15 or older classified as having flourishing, moderate or languishing mental health were 76.9%, 21.6% and 1.5%, respectively. Compared with estimates for other countries, a higher percentage of Canadians were flourishing. In accordance with the complete mental health model, mental health was also assessed in combination with the presence or absence of mental illness (depression; bipolar disorder; generalized anxiety disorder; alcohol, cannabis or other drug abuse or dependence). An estimated 72.5% of Canadians (19.8 million) were classified as having complete mental health; that is they were flourishing and did not meet the criteria for any of the six past 12-month mental or substance use disorders included in the CCHS-MH. Age, marital status, socio-economic status, spirituality and physical health were associated with complete mental health. Men and women were equally likely to be in complete mental health.

  5. Inhibition: Mental Control Process or Mental Resource? (United States)

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan


    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  6. Mental Health Screening Center (United States)

    ... Releases & Announcements Public Service Announcements Partnering with DBSA Mental Health Screening Center These online screening tools are not ... you have any concerns, see your doctor or mental health professional. Depression This screening form was developed from ...

  7. Chronic Illness & Mental Health (United States)

    ... is present. For More Information Share Chronic Illness & Mental Health Download PDF Download ePub Order a free hardcopy ... For more information, see the National Institute of Mental Health (NIMH) booklet on Depression at http://www.nimh. ...

  8. Mental Health and African Americans (United States)

    ... Minority Population Profiles > Black/African American > Mental Health Mental Health and African Americans Poverty level affects mental health ... compared to 120% of non-Hispanic whites. 1 MENTAL HEALTH STATUS Serious psychological distress among adults 18 years ...

  9. Rural Mental Health (United States)

    ... or mental health Peer mentoring School-based mental health services Crisis response Postvention See SAMHSA's Preventing Suicide: A Toolkit ... suicide and promote behavioral health. Offering a Mental ... are in a crisis. To review guidelines for school-based suicide prevention ...

  10. What Is Mental Health? (United States)

    ... Recovery is Possible What Is Mental Health? Mental health includes our emotional, psychological, and social well-being. It affects how we think, feel, and act. It also helps determine how we handle stress, relate to others, and make choices. Mental health is important at every stage of life, from ...

  11. Mental toughness in soccer

    DEFF Research Database (Denmark)

    Diment, Gregory Michael


    In the past decade mental toughness has been discussed as a significant factor in performance in elite sport. Few studies have explored mental toughness from a behavioral perspective, and no comprehensive lists of mental toughness behaviors have been developed. The aim of the study was to produce...... a systematic observation checklist of mental toughness behavior in professional soccer. Consistent with existing studies, the results created a systematic observation instrument containing 15 mental toughness behaviors. Practical implications include goal-setting, game analysis and self-modeling interventions...... where the created checklist could be a practical tool for both coaches and sport psychologists....

  12. Mutation in the AP4M1 Gene Provides a Model for Neuroaxonal Injury in Cerebral Palsy

    NARCIS (Netherlands)

    J.H.M. Verkerk (Annemieke); R. Schot (Rachel); B. Dumee (Belinda); K. Schellekens (Karlijn); S.M.A. Swagemakers (Sigrid); A.M. Bertoli Avella (Aida); M. Leguin (Maarten); J. Dudink (Jeroen); P. Govaert (Paul); A.L. van Zwol (Arjen); J. Hirst (Jennifer); M.W. Wessels (Marja); C.E. Catsman-Berrevoets (Coriene); F.W. Verheijen (Frans); E. de Graaff (Esther); I.F.M. de Coo (René); J.M. Kros (Johan); R. Willemsen (Rob); P.J. Willems (Patrick); P.J. van der Spek (Peter); G.M.S. Mancini (Grazia)


    textabstractCerebral palsy due to perinatal injury to cerebral white matter is usually not caused by genetic mutations, but by ischemia and/or inflammation. Here, we describe an autosomal-recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and at

  13. Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association.



    We report a sibship of two brothers and one sister with the osteoporosis-pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. ...

  14. Sjogren-Larsson syndrome: A rare neurocutaneous disorder

    Directory of Open Access Journals (Sweden)

    Velusamy Subramanian


    Full Text Available Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The pathology behind this syndrome is the failure of degradation of fatty aldehydes. This case is presented for its rarity.

  15. Sjogren-Larsson syndrome: A rare neurocutaneous disorder. (United States)

    Subramanian, Velusamy; Hariharan, Praveen; Balaji, J


    Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The pathology behind this syndrome is the failure of degradation of fatty aldehydes. This case is presented for its rarity.

  16. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy.

    NARCIS (Netherlands)

    G. Weeda (Geert); E. Eveno; I. Donker (Ingrid); W. Vermeulen (Wim); O. Chevalier-Lagente (Odile); A. Taieb; A. Stary; J.H.J. Hoeijmakers (Jan); M. Mezzina; A. Sarasin


    textabstractTrichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and nails, mental retardation, impaired sexual development, and ichthyosis. Photosensitivity has been reported in approximately 50% of the cases, but no skin cancer is associa

  17. Congenital insensitivity to pain with anhidrosis (CIPA): Novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency

    NARCIS (Netherlands)

    Y. Indo (Yasuhiro); S. Mardy (Sek); Y. Miura (Yuichi); A. Moosa (Allie); E.A.R. Ismail (Essam A.); E. Toscano (Ennio); G. Andria (Generoso); V. Pavone (Vito); D.L. Brown (Deborah); A.S. Brooks (Alice); F. Endo (Fumio); I. Matsuda (Ichiro)


    textabstractCongenital insensitivity to pain with anhidrosis is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The human TRKA gene (NTRK1)

  18. Joubert Syndrome - A Case Report

    Directory of Open Access Journals (Sweden)

    Bandichhode S. T.


    Full Text Available Joubert syndrome is a very rare malformation.It is estimated to affect between 1 in 80,000and 1 in 100,000 newborns.Joubert syndromeis an autosomal recessive disorder marked byagenesis of cerebellar vermis, ataxia, hypoto-nia, oculomotor apraxia, neonatal breathingproblems and mental retardation.

  19. The genetic basis of DOORS syndrome : an exome-sequencing study

    NARCIS (Netherlands)

    Campeau, Philippe M.; Kasperaviciute, Dalia; Lu, James T.; Burrage, Lindsay C.; Kim, Choel; Hori, Mutsuki; Powell, Berkley R.; Stewart, Fiona; Felix, Temis Maria; van den Ende, Jenneke; Wisniewska, Marzena; Kayserili, Huelya; Rump, Patrick; Nampoothiri, Sheela; Aftimos, Salim; Mey, Antje; Nair, Lal D. V.; Begleiter, Michael L.; De Bie, Isabelle; Meenakshi, Girish; Murray, Mitzi L.; Repetto, Gabriela M.; Golabi, Mahin; Blair, Edward; Male, Alison; Giuliano, Fabienne; Kariminejad, Ariana; Newman, William G.; Bhaskar, Sanjeev S.; Dickerson, Jonathan E.; Kerr, Bronwyn; Banka, Siddharth; Giltay, Jacques C.; Wieczorek, Dagmar; Tostevin, Anna; Wiszniewska, Joanna; Cheung, Sau Wai; Hennekam, Raoul C.; Gibbs, Richard A.; Lee, Brendan H.; Sisodiya, Sanjay M.


    Background Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals. Methods Through a search o

  20. Epilepsy and Spinocerebellar Ataxia

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available A large consanguinous family from Saudi Arabia with 4 affected children presenting with an autosomal recessive ataxia, generalized tonic-clonic epilepsy and mental retardation is reported from the Institut de Genetique, Universite Louis Pasteur, Illkirch, France; Division of Pediatric Neurology, King Saud University, Riyadh, Saudi Arabia; and other centers.

  1. Disaster mental health

    DEFF Research Database (Denmark)

    Henderson, Silja; Berliner, Peter; Elsass, Peter


    In this chapter we focus on disaster mental health, particularly theoretical and research-based implications for intervention. The field of disaster mental health research is vast and impossible to cover in a single chapter, but we will visit central research, concepts, and understandings within...... disaster mental health and intervention, and refer to further literature where meaningful. We conclude the chapter with recommendations for further research....

  2. Crime and Mental Wellbeing


    Cornaglia, Francesca; Naomi E. Feldman; Leigh, Andrew


    We provide empirical evidence of crime's impact on the mental wellbeing of both victims and non-victims. We differentiate between the direct impact to victims and the indirect impact to society due to the fear of crime. The results show a decrease in mental wellbeing after violent crime victimization and that the violent crime rate has a negative impact on mental wellbeing of non-victims. Property crime victimization and property crime rates show no such comparable impact. Finally, we estimat...

  3. Neurodynamics of mental exploration


    Hopfield, John J


    Thinking allows an animal to take an effective action in a novel situation based on a mental exploration of possibilities and previous knowledge. We describe a model animal, with a neural system based loosely on the rodent hippocampus, which performs mental exploration to find a useful route in a spatial world it has previously learned. It then mentally recapitulates the chosen route, and this intent is converted to motor acts that move the animal physically along the route. The modeling is b...

  4. Salud mental y adicciones


    Boccalari, Paola


    La recientemente reglamentada Ley Nacional de Salud Mental 26.657 plantea amplias reformas en el ámbito de la salud pública. Este escrito se detendrá en uno de los puntos de la ley referido al lugar de las adicciones en las políticas de salud mental. Reflexionará sobre las conexiones entre la salud mental y adicciones. Si bien desde la nueva ley las adicciones forman parte de las políticas de salud mental, la “Y” conectora entre ambas, a la vez que unifica ambos campos, también hace pensar en...

  5. Women's Mental Health (United States)

    ... your relationships, your work, or your life. Some mental illness is caused by trauma, violence, and abuse. Trauma is a terrible event in ... or your feelings. Trauma increases your risk for mental disorder. It may come from u Domestic violence u Child abuse u Incest u Sexual abuse ...

  6. Mental scars of racism. (United States)

    Leiba, Tony

    The over-representation of black and minority ethnic (BME) people in mental health services may reflect their exposure to overt and covert racism, which acts as a 'chronic stressor'. Mental health professionals can help by building positive relationships with their BME patients.

  7. Developing a Mental Timeline. (United States)

    Nesbitt, Donna


    Argues that mental timelines for learning history are analogous to mental mapping for learning geography: both visually represent abstract concepts. Describes the construction of a classroom timeline and activities for fifth- and sixth-grade students that incorporate the use of timelines. Notes reasonable expectations for student progress at this…

  8. Neurodynamics of mental exploration. (United States)

    Hopfield, John J


    Thinking allows an animal to take an effective action in a novel situation based on a mental exploration of possibilities and previous knowledge. We describe a model animal, with a neural system based loosely on the rodent hippocampus, which performs mental exploration to find a useful route in a spatial world it has previously learned. It then mentally recapitulates the chosen route, and this intent is converted to motor acts that move the animal physically along the route. The modeling is based on spiking neurons with spike-frequency adaptation. Adaptation causes the continuing evolution in the pattern of neural activity that is essential to mental exploration. A successful mental exploration is remembered through spike-timing-dependent synaptic plasticity. The system is also an episodic memory for an animal chiefly concerned with locations.


    Directory of Open Access Journals (Sweden)

    M.H. Saheb-Zamani


    Full Text Available Twenty to twenty-five years ago, the Community Mental Health Center (CHMC, had scarcely been heard of. Today, it is indeed a movement, and apparently widespread. A total of ten services considered to be necessary to provide adequate mental health services: (1 in patient, (2 out-patient, (3 partial hospitalization, (4 emergency, (5 consultation, (6 diagn1ostic, (7 rehabilitative, (8 precare and aftercare, (9 training, (10 research and evaluation services. This Concept of Community Mental Health would include as many community agents as possible in co-operative efforts. To the average educated layman, and, unfortunately to most mental health practitioners the community mental health care has become synonymous with the provision of mere psycho-therapy. The community mental health center has not succeeded in becoming inductor of catalytic agent in the growth of its patients, nor has it become significantly involved with the community as a scrcla1 system. These are grim facts. But new hope has begun to appear. It is contained in four revolutions now under way – revolutions in understanding, in research, in nu1ternal and child care and in education for mental health.

  10. Evidence in mental health. (United States)

    Weeks, Susan Mace


    Health practitioners wishing to positively improve health outcomes for their clients have access to a unique set of collated tools to guide their practice. Systematic reviews provide guidance in the form of synthesized evidence that can form the basis of decision making as they provide care for their clients. This article describes systematic reviews as a basis for informed decision making by mental health practitioners. The process of systematic review is discussed, examples of existing systematic review topics relevant to mental health are presented, a sample systematic review is described, and gaps and emerging topics for mental health systematic reviews are addressed.

  11. Hepatitis C: Mental Health (United States)

    ... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

  12. Caring for Mental Disease

    Institute of Scientific and Technical Information of China (English)


    Government increases the funding for treating the mentally ill following cases of uncontrollable violence The Ministry of Health plans to renovate or expand 550 psychiatric hospitals and psychiatric departments

  13. Mentalization, embodiment and narrative

    DEFF Research Database (Denmark)

    Køster, Allan


    of a strong interactive focus, it remains fundamentally rooted in a Cartesian ontology, overlooking embodied, expressive, enactive and sociocultural dimensions of social cognition. Furthermore, since mentalization theory was originally developed as a framework for understanding Borderline Personality Disorder...

  14. Mentalization and social understanding

    DEFF Research Database (Denmark)

    Køster, Allan


    Recently, mentalization theory (Fonagy, Bateman) has risen to fame as a theoretical framework emphasizing social cognition as a key issue in its approach to psychotherapy and psychopathology. In this paper, I review and criticise the social-ontological assumptions made by mentalization theory......, the works of Merleau-Ponty, as well as contemporary phenomenology and enactivism (S. Gallagher, D. Hutto etc.). Since mentalization theory was originally developed as a framework for understanding Borderline Personality Disorder, the article furthermore offers a reinterpretation of the issue of social...... cognition reported in BPD through the lens of the alternative framework. Contrary to the received view, the article suggest that issues of social cognition in BPD should perhaps not be seen as primarily a lack of, or inability to mentalize, but rather as a hyper-sensitivity to the expressive dimension...

  15. La salud mental


    Jiménez Suárez, Sonia; Fundación Valle de Lili


    ¿Qué es la salud mental?/¿Qué son las enfermedades mentales?/¿Cuándo se debe buscar ayuda?/¿La ayuda profesional no es solo para los "locos"?/¿Cómo se tratan las enfermedades mentales?/¿Qué hacen los profesionales de la salud mental?/¿Quiénes ofrecen servicios?/¿Qué esperar en una primera consulta?/¿Para qué el tratamiento con medicamentos?/¿Y qué pasa con los riesgos de sedación y de adicción?/¿En qué consiste la psicoterapia?/¿Y por qué la psicología o la psiquiatría para los niños y adoles...

  16. Mental Mapping: A Classroom Strategy (United States)

    Solomon, Les


    Examines potential uses of mental maps in the classroom by reviewing research efforts, providing an example of the differences between mental maps of two student groups, and suggesting how to use mental maps in the geography curriculum. Mental mapping (or cognitive mapping) refers to individuals' processes of collecting, storing, and retrieving…

  17. The Stigma of Mental Illness (United States)

    Overton, Stacy L.; Medina, Sondra L.


    Stigma surrounding major mental illness creates many barriers. People who experience mental illness face discrimination and prejudice when renting homes, applying for jobs, and accessing mental health services. The authors review the current literature regarding stigma and mental illness. They define stigma and review theories that explain its…

  18. Violence and Mental Illness



    Violence attracts attention in the news media, in the entertainment business, in world politics, and in countless other settings. Violence in the context of mental illness can be especially sensationalized, which only deepens the stigma that already permeates our patients’ lives. Are violence and mental illness synonymous, connected, or just coincidental phenomena? This article reviews the literature available to address this fundamental question and to investigate other vital topics, includi...

  19. Topology and mental processes. (United States)

    McLeay, H


    The study reported here considers the effect of rotation on the decision time taken to compare nonrigid objects, presented as like and unlike pairs of knots and unknots. The results for 48 subjects, 21 to 45 years old, support the notion that images which have a characteristic 'foundation part' are more easily stored and accessed in the brain. Also, there is evidence that the comparison of deformable objects is processed by mental strategies other than self-evident mental rotation.

  20. Mental sundhed i skolen

    DEFF Research Database (Denmark)

    Wistoft, Karen; Grabowski, Dan

    Denne rapport sætter fokus på børn og unges mentale sundhed. Skolen kan gøre en forskel ved at skabe rammerne for en mental sundhedsfremmende skole, der tænker sundhedsbegrebet bredt. Men skolen bør ikke stå alene med ansvaret og derfor er der behov for en samlet strategi. En mentalt sundhedsfrem...

  1. Pakistan mental health country profile. (United States)

    Karim, Salman; Saeed, Khalid; Rana, Mowaddat Hussain; Mubbashar, Malik Hussain; Jenkins, Rachel


    The Republic of Pakistan is a South East Asian country with a population of over 140.7 million. Its population is fast growing and the majority (70%) live in rural areas with a feudal or tribal value system. The economy is dependent on agriculture and 35% of the population live below the poverty line. Islam is the main religion and 'mental illnesses' are stigmatized and widely perceived to have supernatural causes. The traditional healers along with psychiatric services are the main mental health service providers. The number of trained mental health professionals is small as compared to the population demands and specialist services are virtually non-existent. Lack of data on prevalence of various mental illnesses and monitory constraints are the major hurdles in the development of mental health services. A number of innovative programmes to develop indigenous models of care like the 'Community Mental Health Programme' and 'Schools Mental Health Programme' have been developed. These programmes have been found effective in reducing stigma and increase awareness of mental illness amongst the adults and children living in rural areas. Efforts by the government and mental health professionals have led to the implementation of a 'National Mental Health Policy' and 'Mental Health Act' in 2001. These aim at integrating mental health services with the existing health services, improving mental health care delivery and safeguarding the rights of mentally ill people. A favourable political will and the help of international institutions like the World Health Organization are required to achieve these aims.

  2. Mental health informatics

    CERN Document Server

    Song, Insu; Yellowlees, Peter; Diederich, Joachim


    This book introduces approaches that have the potential to transform the daily practice of psychiatrists and psychologists. This includes the asynchronous communication between mental health care providers and clients as well as the automation of assessment and therapy. Speech and language are particularly interesting from the viewpoint of psychological assessment. For instance, depression may change the characteristics of voice in individuals and these changes can be detected by a special form of speech analysis. Computational screening methods that utilise speech and language can detect subtle changes and alert clinicians as well as individuals and caregivers. The use of online technologies in mental health, however, poses ethical problems that will occupy concerned individuals, governments and the wider public for some time. Assuming that these ethical problems can be solved, it should be possible to diagnose and treat mental health disorders online (excluding the use of medication).

  3. Mindfulness og mental sundhed

    DEFF Research Database (Denmark)

    Wistoft, Karen


    Mindfulness is a way to practice 'healthy mindedness' – a form of self help that has been the subject for research and development of a number of new significant self-technologies, therapy and meditation treatment methods. To be mindful can help people to feel more relaxed (serenity) and fully...... alive. The article aims at describing realistic expectations to the contribution of mindfulness to health education work in the field of mental health. The article discuss ways in which mindfulnesss is connected with established health education in the mental health promotion field, and ways in which...... mindfulness breaks with established health education. Interest in utilising mindfulness and mindfulness-inspired methods in health-education intervention has increased in recent years. Mindfulness is seen here as an answer to how to achieve more accepting presence, and thereby a healthier mental life...

  4. Poverty, social stress & mental health. (United States)

    Kuruvilla, A; Jacob, K S


    While there is increasing evidence of an association between poor mental health and the experience of poverty and deprivation, the relationship is complex. We discuss the epidemiological data on mental illness among the different socio-economic groups, look at the cause -effect debate on poverty and mental illness and the nature of mental distress and disorders related to poverty. Issues related to individual versus area-based poverty, relative poverty and the impact of poverty on woman's and child mental health are presented. This review also addresses factors associated with poverty and the difficulties in the measurement of mental health and illness and levels/impact of poverty.

  5. Trastorno mental transitorio

    Directory of Open Access Journals (Sweden)

    Alvaro Burgos Mata


    Full Text Available A mannera de planteamiento teorico se nos llama a considrara el mantenimiento de la distincion existente entre anomalias psiquicas y el Trastorno Mental Transitorio, pues se considera desactualizada la existencia de enfermedades pasajeras y en cambio se insiste en el matis de permanencia que existe en las enfermedades que solo a veces tienen menifestaciones.As a theorical plan, we are called to reflect on the maintenance of the distinction made between psychic anomalies and the transitory mental disorder, because the existence of temporal diseases has been surpassed y and now it is insisted on the permanency of diseases which are occassionally manifested.

  6. Paranormal experiences, mental health and mental boundaries, and psi


    Rabeyron, Thomas; Watt, Caroline


    Previous research has suggested that paranormal beliefs and experiences are associated with thinner mental boundaries and traumas during childhood. This paper examines more thoroughly the relationship between paranormal experiences, mental health and boundaries, and psi abilities. One hundred and sixty two participants completed questionnaires about paranormal experiences (AEI), mental health (MHI-17), mental boundaries (BQ-Sh), traumas during childhood (CATS) and life-changing events (LES). ...

  7. Issues in Mental Health Counseling with Persons with Mental Retardation. (United States)

    Prout, H. Thompson; Strohmer, Douglas C.


    Reviews mental-health issues concerning persons with mental retardation, particularly as these issues apply to mental-health counseling. Included in this review is a discussion of the prevalence of psychopathology, types of problems presented, issues in clinical bias, access to community services, assessment techniques, and specific…

  8. School Mental Health Resources and Adolescent Mental Health Service Use (United States)

    Green, Jennifer Greif; McLaughlin, Katie A.; Alegria, Margarita; Costello, E. Jane; Gruber, Michael J.; Hoagwood, Kimberly; Leaf, Philip J.; Olin, Serene; Sampson, Nancy A.; Kessler, Ronald C.


    Objective: Although schools are identified as critical for detecting youth mental disorders, little is known about whether the number of mental health providers and types of resources that they offer influence student mental health service use. Such information could inform the development and allocation of appropriate school-based resources to…

  9. Mental Health and Heart Health (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Mental Health and Heart Health Updated:Nov 10,2015 For years, doctors thought the connection between mental health and heart health was strictly behavioral – such as ...

  10. Dystonia: Emotional and Mental Health (United States)

    ... Support Frequently Asked Questions Faces of Dystonia Emotional & Mental Health Although dystonia is a movement disorder that impacts ... emotion as well as muscle movement. For years, mental health professionals have recognized that coping with a chronic ...

  11. National Institute of Mental Health (United States)

    ... to content Home Health & Education Health & Education Home Mental Health Information Publications Educational Resources Clinical Trials – Information for ... Gordon discusses NIMH priorities and future directions in mental health research. More RDoC Office Hours Are you a ...

  12. Mental Health Treatement Facilities Locator (United States)

    U.S. Department of Health & Human Services — An online resource for locating mental health treatment facilities and programs supported by the Substance Abuse and Mental Health Services Administration (SAMHSA)....

  13. Incompatibility and Mental Fatigue (United States)

    Herzog, Thomas R.; Hayes, Lauren J.; Applin, Rebecca C.; Weatherly, Anna M.


    A straightforward prediction from attention restoration theory is that the level of incompatibility in a person's life should be positively correlated with that person's level of mental (or directed attention) fatigue. The authors tested this prediction by developing a new self-report measure of incompatibility in which they attempted to isolate…

  14. Carga Mental e Ergonomia

    Directory of Open Access Journals (Sweden)

    Fábio Corrêa


    Full Text Available Este estudo investiga a utilidade e a possibilidade de uso da base teórica de Carga Mental no trabalho, em uma situação de trabalho específica no que se refere aos seus aspectos ergonômicos.

  15. Caring for Mental Disease

    Institute of Scientific and Technical Information of China (English)

    LI LI


    @@ The Ministry of Health plans to renovate or expand 550 psychiatric hospitals and psychiatric departments in comprehensive hospitals across the country within two years,said Vice Minister Yin Li.It's part of the country's latest effort to combat the growing problem of mental illness.

  16. Mental sundhed i skolen

    DEFF Research Database (Denmark)

    Wistoft, Karen

    Baggrund: Skolebørns opfattelse af sundhed har i høj grad noget med deres selvbilleder, trivsel og sociale inklusion at gøre. Det viser en lang række nyere undersøgelser, der alle peger på, at det er nødvendigt at skærpe opmærksomheden på børn og unges mentale sundhed. Internationalt er der...... udviklet og afprøvet en række pædagogiske programmer, der kan bruges til at igangsætte aktiviteter, der fremmer børn og unges mentale sundhed i skolen. Især i USA, Australien og Storbritannien har der været fokus på evidensbaseret praksis og praksisbaseret evidens i denne sammenhæng. I Danmark har man ikke...... på sammen måde tilgængelig systematiseret viden herom. Sundhedsstyrelsen har gennem de senere år prioriteret indsatser og fremskrivning af evidensgrundlag til fremme af mental sundhed højt. Betydningen af børns mentale sundhed og overvejelser om, hvilken slags evidens der er behov for på dette område...

  17. Mental retirement and schooling

    DEFF Research Database (Denmark)

    Bingley, Paul; Martinello, Alessandro


    We assess the validity of differences in eligibility ages for early and old age pension benefits as instruments for estimating the effect of retirement on cognitive functioning. Because differences in eligibility ages across country and gender are correlated with differences in years of schooling...... of the “mental retirement” effects which have recently been found...

  18. Mini mental state examination

    DEFF Research Database (Denmark)

    Kørner, Ejnar Alex; Lauritzen, Lise; Wang, August;


    INTRODUCTION: The Mini Mental State Examination (MMSE) is widely used in Denmark, but often in non-validated versions. In 2000 a cross-sectional workgroup decided on a new common version of the MMSE with a corresponding manual, which is validated for the first time in the present study. MATERIALS...

  19. Recovery from mental illness

    DEFF Research Database (Denmark)

    Petersen, Kirsten Schultz; Friis, Vivi Soegaard; Haxholm, Birthe Lodahl;


    Mental health services strive to implement a recovery-oriented approach to rehabilitation. Little is known about service users' perception of the recovery approach. The aim is to explore the service user's perspectives on facilitators and barriers associated with recovery. Twelve residents living...

  20. Improving Mental Health in Schools (United States)

    Rossen, Eric; Cowan, Katherine C.


    Students do not leave their mental health at the front door when they come to school. From wellness to serious illness, a student's mental health status is integral to how they think, feel, interact, behave, and learn. Decades of research and experience have laid a solid foundation and framework for effectively providing mental health…

  1. What Is Infant Mental Health? (United States)

    Osofsky, Joy D.; Thomas, Kandace


    Unfortunately, the term "infant mental health" can be confusing for some people because it may be understood as translating into "mental illness." Others may not appreciate that babies and toddlers have the capacity to experience complex emotions. The Guest Editors of this issue of the Journal explore the meaning of infant mental health.

  2. Cannabis use and mental health

    NARCIS (Netherlands)

    van Gastel, W.A.


    Cannabis use has been implicated as a risk factor for mental health problems, (subclinical) psychotic symptoms in particular. If cannabis use was a cause of these problems, cessation would lead to improved public mental health. If cannabis use was a mere consequence of a predisposition for mental he

  3. Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Shamsudheen Karuthedath Vellarikkal


    Full Text Available Dystrophic epidermolysis bullosa simplex (DEB is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES. Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

  4. Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Shamsudheen Karuthedath Vellarikkal


    Full Text Available Dystrophic epidermolysis bullosa simplex (DEB is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES. Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.


    Directory of Open Access Journals (Sweden)

    L. V. Osadcha


    Full Text Available Purpose. The article is devoted to clarifying the role of physicality and psycho-physical characteristics of a person as a preconditions of the mentality forming. It is conducted a retrospective analysis of discourse on the mentality, the history of the concept, its temporal characteristics and collective conditioning. The concept of mentality has been widely studied in various fields of socio-humanities such as: history, psychology, and even marginal context of scientific discourses, including the esoteric. This study attempted to analyse the mentality phenomenon through the prism of the concept of experience. Methodology. The concept of experience was acquired by essential justification through the representatives of the phenomenological approach - the late Edmund Husserl, Maurice Merleau-Ponty, Bernhard Valdenfels. On the other hand the concept of mentality as a form of collective unconscious experience was entered to the scientific vocabulary by the representatives of the French historical science - M. Bloch, L. Febvre, J. Le Goff and others. At the intersection of these two methods, historical and phenomenological, the genetic method has been established – as a history of coverage and experience of internalization. Thanks to the application of genetic method the transition of phenomenon into the concept was examined. Novelty. The problem of change dynamics of mental phenomenon, in particular psycho-physical nature of a person, which has been only mentioned in F. Braudel works but has not received the adequate theoretical coverage, is analysed. To explain the practices of physicality and causality of this factor the action component of the cultural the overview of developments of such authors as V. Rozin (2005, M. Epstein (2005, N. Brunov (2003, A. Soares, M. Farhangmehr, A. Shoham (2007, D. Vaskul, F. Vannini Hospital (2012 was committed. Conclusions. The transition to paradoxical behaviour that is oriented on sign, and not on signalling

  6. Neural mechanisms of mental fatigue. (United States)

    Ishii, Akira; Tanaka, Masaaki; Watanabe, Yasuyoshi


    Fatigue is defined as a decline in the ability and efficiency of mental and/or physical activities that is caused by excessive mental and/or physical activities. Fatigue can be classified as physical or mental. Mental fatigue manifests as potentially impaired cognitive function and is one of the most significant causes of accidents in modern society. Recently, it has been shown that the neural mechanisms of mental fatigue related to cognitive task performance are more complex than previously thought and that mental fatigue is not caused only by impaired activity in task-related brain regions. There is accumulating evidence supporting the existence of mental facilitation and inhibition systems. These systems are involved in the neural mechanisms of mental fatigue, modulating the activity of task-related brain regions to regulate cognitive task performance. In this review, we propose a new conceptual model: the dual regulation system of mental fatigue. This model contributes to our understanding of the neural mechanisms of mental fatigue and the regulatory mechanisms of cognitive task performance in the presence of mental fatigue.

  7. Mental Health Ethnography

    DEFF Research Database (Denmark)

    Ringer, Agnes


    In 2010, I began a PhD study to examine how professionals and patients talked to—and about—each other in mental health institutions in Denmark. One year later, I found myself chain-smoking, dressed in baggy clothing, and slouching on a sofa in a closed psychiatric ward. I had not myself been hosp...... during the study, and I discuss different strategies of access. The case also contains some practical advice and lessons learned to consider for new researchers and students looking to do ethnographies in institutional settings....... hospitalized, but to get inside the contemporary psychiatric institution and to participate in the social world of patients and professionals, I had to experiment with different ethnographic approaches. Ethnographies of mental health have become increasingly rare, and much research on language in psychiatric...

  8. Postpartum Mental Syndromes


    Seltzer, Allan


    Recent evidence suggests that parturition is a precipitating factor against a background of an inherited or acquired host constitution predisposing to emotional disorder. Postpartum mental illness is a spectrum of syndromes ranging from the fairly benign transient “blues” to more severe affective, organic or schizophreniform psychoses. Neuroendocrine factors may be the underlying etiologic agent. Treatment may involve support and reassurance, formal psychotherapy or psychotropic and somatic t...

  9. Mindfulness og mental sundhed


    Wistoft, Karen


    Mindfulness is a way to practice 'healthy mindedness' – a form of self help that has been the subject for research and development of a number of new significant self-technologies, therapy and meditation treatment methods. To be mindful can help people to feel more relaxed (serenity) and fully alive. The article aims at describing realistic expectations to the contribution of mindfulness to health education work in the field of mental health. The article discuss ways in which mindfulnesss is ...

  10. Exercise Prevents Mental Illness (United States)

    Purnomo, K. I.; Doewes, M.; Giri, M. K. W.; Setiawan, K. H.; Wibowo, I. P. A.


    Multiple current studies show that neuroinflammation may contribute to mental illness such as depression, anxiety, and mood disorder. Chronic inflammation in peripheral tissues is indicated by the increase of inflammatory marker like cytokine IL-6, TNF-α, and IL-1β. Pro-inflammatory cytokine in peripheral tissues can reach brain tissues and activate microglia and it causes neuroinflammation. Psychological stress may led peripheral and central inflammation. Activated microglia will produce pro-inflammatory cytokine, ROS, RNS, and tryptophan catabolizes. This neuroinflammation can promote metabolism changes of any neurotransmitter, such as serotonin, dopamine, and glutamate that will influence neurocircuit in the brain including basal ganglia and anterior cingulated cortex. It leads to mental illness. Exercise give contribution to reduce tissue inflammation. When muscle is contracting in an exercise, muscle will produce the secretion of cytokine like IL-6, IL-1ra, and IL-10. It will react as anti-inflammation and influence macrophage, T cell, monosit, protein Toll-Like Receptor (TLR), and then reduce neuroinflammation, characterised by the decrease of pro-inflammatory cytokine and prevent the activation of microglia in the brain. The objective of the present study is to review scientific articles in the literature related to the contribution of exercise to prevent and ease mental illness.

  11. New percepts via mental imagery?

    Directory of Open Access Journals (Sweden)

    Fred Walter Mast


    Full Text Available We are able to extract detailed information from mental images that we were not explicitly aware of during encoding. For example, we can discover a new figure when we rotate a previously seen image in our mind. However, such discoveries are not really new but just new interpretations. In two recent publications, we have shown that mental imagery can lead to perceptual learning (Tartaglia et al., 2009, 2012. Observers imagined the central line of a bisection stimulus for thousands of trials. This training enabled observers to perceive bisection offsets that were invisible before training. Hence, it seems that perceptual learning via mental imagery leads to new percepts. We will argue, however, that these new percepts can occur only within known models. In this sense, perceptual learning via mental imagery exceeds new discoveries in mental images. Still, the effects of mental imagery on perceptual learning are limited. Only perception can lead to really new perceptual experience.

  12. Light Therapy in Mental Hospitals. (United States)

    Cormac, H D


    The position of actinotherapy in Mental Hospitals in this country is reviewed. An investigation of the results of ultra-violet irradiation in mental disorders at Parkside Mental Hospital is described and it is shown that certain types of the psychoses appear to benefit. The physiological action of actinic rays in relation to mental disorders is discussed and their mode of action on the nervous system suggested. Reference is made to substances which sensitize the body tissues to sunlight and ultra-violet radiation. An allusion is made to glass, penetrable by a portion of the actinic rays, and its uses. The need for ultra-violet ray apparatus in every mental hospital is urged both for treatment of mental and physical conditions and for the study of its action.

  13. The stigma of mental illness


    Kordosi A; Saridi M; Souliotis K


    Introduction:The stigma of mental illness is not a modern phenomenon, but it can now be approached scientifically. The stigma, because of the mental illness which characterizes a person, can be explained by the natural propensity of man to deliver biased and stereotyped estimates to phenomena he cannot explain, accept or face. Methodology:This study is an attempt to describe the concept of stigma and the impact of the stigma of mental illness in the personal and social life of the...

  14. Stigmatization and mental health

    Directory of Open Access Journals (Sweden)

    Gulsum Ozge Doganavsargil Baysal


    Full Text Available Stigmatizasyon represent a chronic negative interaction with the environment that most of people with a of diagnosis mental disorders. Different types of stigma may have harmful effects. Poor psychological well being, poor quality of life and poor self esteem are related stigmatization. In this article, definition and mechanism of stigmatization, influenced factors and consequences of stigmatization are reviewed. Stigmatization is a modifiable environmental risk factor. Integrating approaches against stigma in treatment may represent cost-effective way to reduce the risk of relapse and poor outcome occasioned by chronic exposure to stigma. [Archives Medical Review Journal 2013; 22(2.000: 239-251

  15. Los calculistas mentales

    Directory of Open Access Journals (Sweden)

    Salvador Galindo Uribarri


    Full Text Available Los calculistas mentales, sujetos que realizan en un instante complejas operaciones aritméticas, han desarrollado habilidades que nos parecen -al resto de mortales- sorprendentes y aún increíbles. Estos sujetos se distinguen por su capacidad de concentración e increíble memoria y además emplean procedimientos de cálculo dis - tintos a los que ordinariamente ocupamos en nuestra vida cotidiana. Este trabajo trata sobre dichos procedimientos mostrando que difieren de los algoritmos tradicionales.


    Directory of Open Access Journals (Sweden)

    Alexander Oktyabrinovich Prokhorov


    Full Text Available Since the time of statement of the problem of states in psychology, the study of “sensuous” tissue – the mental state representation-takes a fundamental meaning. The problem is concluded in the following questions: “How is mental state represented in the consciousness of an individual?”, “What is the specificity of the mental state representation as distinguished from the subject-matter representation?”, “What are the mechanisms of the mental state representation occurrence and the peculiarities of its dynamics? The study of the mental state representation will allow to explain its specificity and difference from the figurative representation, the peculiarities of state explication as a representation in the consciousness and its relation with other elements of consciousness, will allow to show the regularities of the mental state representation development and its dynamics, factors, which influence the specificity of its occurrence, the regulatory role of the state representation in the vital function. From these perspectives, the article presents the results of the study of spatiotemporal characteristics of the mental state representation; reveals the peculiar features of the spatiotemporal organization of mental state representations: Relieves, specificity, magnitude, variability of indicators, changes of structural characteristics in time spans; considers the age-specific peculiar features of the spatiotemporal organization of mental state representations in terms of organization, stability, coherence and differentiated nature of spatiotemporal structures with the representatives of certain age groups.

  17. Teaching Mental Abacus Calculation to Students with Mental Retardation (United States)

    Shen, Hong


    The abacus is a calculating tool that has been used in Asia for thousands of years. Mental abacus calculation is a skill in which an abacus image in the mind is used without the actual physical manipulation of the abacus. Using this method, people can perform extremely rapid and accurate mental calculations. Research indicates that abacus training…


    Directory of Open Access Journals (Sweden)

    Gulshat Tavkil’evna Shavalieva


    Full Text Available This article deals with the peculiarities of structural and functional organization of mental states of three age groups’ respondents. Depending on the degree of exposure in primary school children, adolescents, and adults similar in nature mental states, but different in their stability and structure are observed. It was found that children with different levels of mental development of a completely different operating parameters of the states – mental proces-ses, physiological reactivity, feelings and behavior. The specifics of the states and the reliefs showed different levels of mental activity of children of three age groups. The structural and functional organization of mental states to identify the different structures of blocks, their interconnectivity, and they differ in the degree of involvement of the parameters of mental states to each other. Each group revealed a different level of mental activity. The differences in the mechanisms of perception of children of three age groups depending on the level of mental development.The aim is to study the features of mental conditions of «school age» children, their structural and functional organization of the perception of the artistic image «Before the Wedding» picture of the famous Russian artist F.S. Zhuravlev’s «Before the Wedding». Identification of the mechanisms of perception of the image and the features state structures of subjects.Method and methodology of work. Research carried out on the basis of a systematic methodology and the theory of activity developed by Vygotsky, Leontiev, Luria and A. Brushlinskii subject approach, SL Rubinstein and also theoretical principles and provisions of the concept of mental conditions of the person (A.O. Prohorov and concepts of color (J.W. Go-ethe, P.V. Yanshin et al.. The material of the study served as a theoretical analysis of the general and special literature on the perception of color and artistic images

  19. American Christian Engagement With Mental Health and Mental Illness. (United States)

    Kinghorn, Warren A


    Although religious belief and practice are relevant to mental health outcomes, many clinicians lack knowledge of particular religious traditions required to make informed judgments about referral to and collaboration with faith-based organizations and clinicians. This Open Forum examines five diverse American Christian approaches to mental health and mental illness-pastoral care and counseling, biblical counseling, integrationism, Christian psychology, and the work of the Institute for the Psychological Sciences--that are relevant for contemporary mental health service delivery. Each of these movements is briefly described and placed in historical, conceptual, and organizational context. Knowledge of the diverse and varied terrain of American Christian engagement with mental health care can inform clinicians' interactions with faith-based providers, clarify opportunities for responsible collaboration, and provide important insight into religious subcultures with faith-based concerns about contemporary psychiatric care.

  20. Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review. (United States)

    al-Hemidan, A I; al-Hazzaa, S A


    Richner-Hanhart syndrome (Tyrosinemia Type II) is an autosomal recessive disorder of amino acid metabolism characterized by ocular changes, painful palmoplantar hyperkeratosis, and mental retardation. Serum tyrosine increases due to tyrosine aminotransferase deficiency resulting in the deposition of tyrosine crystals in the cornea and in corneal inflammation. Patients are often misdiagnosed as having herpes simplex keratitis. We report on a child who presented with bilateral keratitis secondary to Tyrosinemia Type II diagnosed as herpes simplex keratitis.

  1. Disease: H01001 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01001 COACH syndrome COACH syndrome is a rare autosomal recessive disorder with cerebellar vermis hypoplasi...a, oligophrenia, ataxia, coloboma, and hepatic fibrosis. The vermis hypoplasia comp...osis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation. Am J Med Genet 64:514-20 (... Caruso ML, Panella C, Vajro P, Guanti G COACH syndrome: report of two brothers with congenital hepatic fibr

  2. Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene.


    Waterham, H. R.; Wijburg, F.A.; Hennekam, R. C.; Vreken, P; Poll-The, B T; Dorland, L.; Duran, M.; Jira, P.E.; Smeitink, J. A.; Wevers, R. A.; Wanders, R J


    Smith-Lemli-Opitz syndrome is a frequently occurring autosomal recessive developmental disorder characterized by facial dysmorphisms, mental retardation, and multiple congenital anomalies. Biochemically, the disorder is caused by deficient activity of 7-dehydrocholesterol reductase, which catalyzes the final step in the cholesterol-biosynthesis pathway-that is, the reduction of the Delta7 double bond of 7-dehydrocholesterol to produce cholesterol. We identified a partial transcript coding for...

  3. Marinesco-Sjogren Syndrome With Sensori Neural Deafness And Primary Optic Atrophy

    Directory of Open Access Journals (Sweden)

    Aleem M A


    Full Text Available Marinesco-Sjogren syndrome (MSS is a rare genetically determined disorder characterised by bilateral cataract, cerebellar ataxia and mental deficiency. The pattern of inheritance is autosomal recessive but it may be variable. In MSS association of hyperlactacidaemia and hypopyruvicaemia, a defective oxidative phosphorylation in mitochondria, is supposed. We are reporting three patients of MSS along with sensorineural deafness and optic atrophy from a single Indian family.

  4. Joubert syndrome: large clinical variability and a unique neuroimaging aspect Síndrome de Joubert: grande variabilidade clínica e uma neuroimagem característica


    Emília Katiane Embiruçu Leão; Marcília Martyn Lima; Otacílio de Oliveira Maia Júnior; Juliana Parizotto; Fernando Kok


    Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g, pigmentary retinopathy, oculomotor apraxia and nystagmus), renal cysts and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. At least seven JS loci have been determined and five genes identified. Herein, we report five children, belonging to independent families, with JS: they s...

  5. Anaesthetic management of a child with panthothenate kinase-associated neurodegeneration

    Directory of Open Access Journals (Sweden)

    Renu Sinha


    Full Text Available Panthothenate kinase-associated neurodegeneration (PKAN (Hallervorden-Spatz disease is a rare autosomal recessive chromosomal disorder characterised by progressive neuroaxonal dystrophy. The characteristic features include involuntary movements, rigidity, mental retardation, seizures, emaciation. The anaesthetic concerns include difficult airway, aspiration pneumonia, dehydration, and post-operative respiratory, and renal insufficiency. We report successful anaesthetic management of a 9-year-old intellectually disabled male child with PKAN, scheduled for ophthalmic surgery under general anaesthesia.

  6. Mental Models: A Robust Definition (United States)

    Rook, Laura


    Purpose: The concept of a mental model has been described by theorists from diverse disciplines. The purpose of this paper is to offer a robust definition of an individual mental model for use in organisational management. Design/methodology/approach: The approach adopted involves an interdisciplinary literature review of disciplines, including…

  7. Child and Adolescent Mental Health (United States)

    ... allows youth to text live with a mental health professional. Crisis Text Line : help is available 24 hours a day throughout the US by texting START to 741741 More ... that cover a variety of mental health topics! An expert in scientific and health issues ...

  8. Chronic diseases and mental disorder.

    NARCIS (Netherlands)

    Verhaak, P.F.M.; Heijmans, M.J.W.M.; Peters, L.; Rijken, M.


    The aim of this study was to achieve a better understanding of the relationship between chronic medical illness and mental distress. Therefore, the association between chronic medical illness and mental distress was analysed, taking into account the modifying effects of generic disease characteristi

  9. Teenage Pregnancy and Mental Health

    Directory of Open Access Journals (Sweden)

    Jacqueline Corcoran


    Full Text Available This article reviews the intersection between adolescent pregnancy and mental health. The research involving mental health risks for adolescent pregnancy and for parents who are teenagers are discussed. Depression and conduct disorder have emerged with the most attention. Research-based treatment of these disorders in adolescents is presented.

  10. Mental Health Care: Who's Who (United States)

    ... Living Listen Español Text Size Email Print Share Mental Health Care: Who's Who Page Content Article Body Psychiatrist: ... degree in psychology, counseling or a related field. Mental Health Counselor: Master’s degree and several years of supervised ...

  11. What Do Mental Terms Mean? (United States)

    Moore, Jay


    Psychologists and philosophers have long been interested in two questions: (a) What do mental terms mean? and (b) what role do mental terms play in explanations of behavior? In the current sketch I review how mediational neobehaviorism, cognitive psychology, and the radical behaviorism of B. F. Skinner address these questions. In so doing, I seek…

  12. International Students and Mental Health (United States)

    Forbes-Mewett, Helen; Sawyer, Anne-Maree


    Since the early 2000s, reports of increased rates of mental ill health among young people worldwide have received much attention. Several studies indicate a greater incidence of mental health problems among tertiary students, compared with the general population, and higher levels of anxiety, in particular, among international students compared…

  13. VA National Mental Health Statistics - 2015 (United States)

    Department of Veterans Affairs — VAMC-level statistics on the prevalence, mental health utilization, non-mental health utilization, mental health workload, and psychological testing of Veterans with...

  14. Juvenile justice mental health services. (United States)

    Thomas, Christopher R; Penn, Joseph V


    As the second century of partnership begins, child psychiatry and juvenile justice face continuing challenges in meeting the mental health needs of delinquents. The modern juvenile justice system is marked by a significantly higher volume of cases, with increasingly complicated multiproblem youths and families with comorbid medical, psychiatric, substance abuse disorders, multiple family and psychosocial adversities, and shrinking community resources and alternatives to confinement. The family court is faced with shrinking financial resources to support court-ordered placement and treatment programs in efforts to treat and rehabilitate youths. The recognition of high rates of mental disorders for incarcerated youth has prompted several recommendations for improvement and calls for reform [56,57]. In their 2000 annual report, the Coalition for Juvenile Justice advocated increased access to mental health services that provide a continuum of care tailored to the specific problems of incarcerated youth [58]. The specific recommendations of the report for mental health providers include the need for wraparound services, improved planning and coordination between agencies, and further research. The Department of Justice, Office of Juvenile Justice and Delinquency Prevention has set three priorities in dealing with the mental health needs of delinquents: further research on the prevalence of mental illness among juvenile offenders, development of mental health screening assessment protocols, and improved mental health services [59]. Other programs have called for earlier detection and diversion of troubled youth from juvenile justice to mental health systems [31,56]. Most recently, many juvenile and family courts have developed innovative programs to address specific problems such as truancy or substance use and diversionary or alternative sentencing programs to deal with first-time or nonviolent delinquents. All youths who come in contact with the juvenile justice system

  15. [Mentalization and theory of mind]. (United States)

    Wyl, Agnes


    Both concepts, mentalization and the theory of mind, describe metacognitive processes. Mentalization mainly concerns the reflection of affective mental states. In contrast, theory of mind focuses on epistemic states such as beliefs, intentions and persuasions. Gender differences have proved to be relevant for both, the development of mentalization and the theory of mind. However, there are few studies and findings are inconsistent. In an own study, we investigated the relationship between early competences in metacognition (tested in a false-belief-task second order) and narrative skills of kindergarten children. Results show that children who had successfully passed the theory of mind test tended to face conflicts more directly in the stories. In consequence, these children showed less narrative avoidance. However, differences were only found in girls and not in boys. The precise understanding of developmental differences in metacognition between girls and boys may be an important aspect with regards to improving mentalization based therapy of children.

  16. [Anomie and public mental health]. (United States)

    Parales-Quenza, Carlos J


    This article uses the concept of anomie for understanding public mental-health issues and constructing strategies aimed at promoting health and preventing disease. Studying anomie involves many definitions and approaches; this article conceptualises anomie as dérréglement or derangement and as a total social fact as its effects and consequences are pervasive across all areas of human experience. The article suggests the pertinence of the concept to public health based on several authors' observations depicting Latin-America as being a set of anomic societies and Colombia as the extreme case. Current definitions of mental health in positive terms (not just as being the absence of mental illness) validate the need for considering anomie as an indicator of public mental health. The article proposes that if anomie expresses itself through rules as basic social structure components, then such rules should also be considered as the point of intervention in promoting mental health.

  17. Movilidad y representaciones mentales


    Cortellezzi, Mónica M.


    Nos movemos en el mundo y nos contactamos con él a través de los informativos de la televisión, o los de la radio y prensa. Decimos a menudo que tenemos ideas sobre los lugares geográficos, lo cual significa, por supuesto, tener de ellos algún conocimiento o imagen. En definitiva, estamos hablando de los rastros que quedan en nuestros archivos mentales, o sea que los lugares geográficos no están sólo  fuera de nosotros con la existencia física que les pertenece, sino que, están también dentro...

  18. How to be Brilliant at Mental Arithmetic

    CERN Document Server

    Webber, Beryl


    How to be Brilliant at Mental Arithmetic addresses the twin pillars of mental arithmetic - mental recall and mental agility. Mental recall depends on familiarity with number bonds and plenty of opportunity to practise. Mental agility depends more on confidence with the number system and the four operations. Using the worksheets in this book, students will learn about: tens and units; addition, subtraction, multiplication and division; addition shortcuts; product squares; quick recall; number se

  19. Somali Refugees' Perceptions of Mental Illness. (United States)

    Bettmann, Joanna E; Penney, Deb; Clarkson Freeman, Pamela; Lecy, Natalie


    Nearly 13% of the U.S. population is comprised of foreign-born individuals, with Somalis constituting one of the largest resettled groups. Research suggests that, among Somali refugees, rates of mental illness are high. Yet research shows Somalis underutilize mental health services. Understanding their perceptions of mental illness and its cures may help practitioners to design more effective treatments for this population. Thus, this pilot study investigated Somali refugees' perceptions of mental illness and its treatments. Using purposive sampling, this qualitative study interviewed 20 Somali refugees using a semi-structured interview guide. Qualitative analysis yielded participants' perceptions of mental illness through their descriptions of physical symptoms accompanying mental illness, the stigma of mental illness, causes of mental illness, medical and non-medical treatments for mental illness, spirit possession causing mental illness, and the Qur'an as treatment for mental illness. Such information may help practitioners in the United States approach Somali clients in the most culturally coherent manner.

  20. Mental Health: Overcoming the Stigma of Mental Illness (United States)

    ... social activities or trouble finding housing Bullying, physical violence or harassment Health insurance that doesn't adequately cover your mental illness treatment The belief that you'll never be ...

  1. Higiene mental de guerra

    Directory of Open Access Journals (Sweden)

    Durval Marcondes


    Full Text Available Uma das caraterísticas da presente guerra é a de ser, mais que qualquer outra, uma guerra psicológica. Embora o emprego dos recursos psicológicos como arma de guerra não constitua nenhuma novidade, nunca êle assumiu, como agora, um papel de tão alta importância. O A. refere-se à utilização dos métodos psicológicos de guerra desde as épocas mais remotas, salientando que, com o correr dos tempos, foi-se deslocando para o terreno científico aquilo que antes era simples magia ou intuição. Enumera os métodos ofensivos e defensivos essenciais da guerra psicológica, focalizando o papel desempenhado pela propaganda e pelo medo. Examina como a Alemanha se utilizou dos conhecimentos psicológicos em seu esforço de guerra, tanto no preparo psíquico individual como coletivo. Afirma que cabe aos psicólogos e psiquiatras das Nações Unidas oferecer às autoridades os meios de ação para o mesmo fim, o que não quer dizer que precisemos copiar servilmente os métodos alemães. Passa a referir-se aos recursos que a moderna psiquiatria pode oferecer nesse sentido, mostrando que ela desenvolveu técnicas e sistemas de trabalho que dilataram sobremodo o campo de suas atividades. Ela não está mais limitada ao âmbito estreito das enfermarias e das salas de consulta, mas transborda numa intervenção mais direta sobre o ambiente social. De simples especialidade médica circunscrita à cura individual das psicopatias, ela se erigiu em arma social de elevado alcance, cujo valor a presente guerra veio encarecer. O A. lembra, enfim, a importância do trato psicológico das populações no período de após-guerra. Um simples tratado de paz não cria as condições necessárias a uma sadia atitude mental coletiva. À higiene mental caberá um papel relevante no futuro reajustamento psíquico dos povos, o qual, para sua verdadeira consolidação, deverá assentar sobre bases científicas e humanas.

  2. Cognitive mapping in mental time travel and mental space navigation. (United States)

    Gauthier, Baptiste; van Wassenhove, Virginie


    The ability to imagine ourselves in the past, in the future or in different spatial locations suggests that the brain can generate cognitive maps that are independent of the experiential self in the here and now. Using three experiments, we asked to which extent Mental Time Travel (MTT; imagining the self in time) and Mental Space Navigation (MSN; imagining the self in space) shared similar cognitive operations. For this, participants judged the ordinality of real historical events in time and in space with respect to different mental perspectives: for instance, participants mentally projected themselves in Paris in nine years, and judged whether an event occurred before or after, or, east or west, of where they mentally stood. In all three experiments, symbolic distance effects in time and space dimensions were quantified using Reaction Times (RT) and Error Rates (ER). When self-projected, participants were slower and were less accurate (absolute distance effects); participants were also faster and more accurate when the spatial and temporal distances were further away from their mental viewpoint (relative distance effects). These effects show that MTT and MSN require egocentric mapping and that self-projection requires map transformations. Additionally, participants' performance was affected when self-projection was made in one dimension but judgements in another, revealing a competition between temporal and spatial mapping (Experiment 2 & 3). Altogether, our findings suggest that MTT and MSN are separately mapped although they require comparable allo- to ego-centric map conversion.

  3. Telepsychiatry and school mental health. (United States)

    Grady, Brian J; Lever, Nancy; Cunningham, Dana; Stephan, Sharon


    The provision of mental health services in schools has been one effective strategy for reaching out to a greater number of youth to identify and provide treatment for mental health issues. With the increasing challenges related to shortages in child and adolescent psychiatrists, it is critical to develop models of care that can maximize a full range of mental health services for all children and adolescents who need them. Telehealth offers an innovative distance technology strategy to effectively and efficiently provide access to psychiatric services in schools. Telepsychiatry has the potential to better link and enhance the provision of health services, and can be particularly beneficial in addressing geographic distance and/or capacity issues. This article describes the clinical, educational, and administrative uses of telemental health in the school environment with mental health professionals and staff.

  4. Student Attitudes Toward Mental Illness (United States)

    Hare-Mustin, Rachel T.; Garvine, Richard


    Inquiry into the initial attitudes toward mental illness of students taking an abnormal psychology class indicates students' concerns and preconceptions and provides a basis for shaping the course to respond to student needs. (JH)

  5. The Autonomy of Mental Models. (United States)

    Fischbein, Efraim; And Others


    Described is research which sought to prove the hypothesis that mental models tend to preserve their autonomy with regard to the originals they are meant to represent. The results of this investigation involving 200 Israeli students are presented. (CW)

  6. A roadmap for mental health. (United States)

    Moore, Alison


    The Five Year Forward View could be a turning point in the battle to get mental health parity with physical health, address long waiting times and unmet need, and ensure people get care close to home.

  7. 49 CFR 1572.109 - Mental capacity. (United States)


    ... 49 Transportation 9 2010-10-01 2010-10-01 false Mental capacity. 1572.109 Section 1572.109... ASSESSMENTS Standards for Security Threat Assessments § 1572.109 Mental capacity. (a) An applicant has mental incapacity, if he or she has been— (1) Adjudicated as lacking mental capacity; or (2) Committed to a...

  8. Mental life in the space of reasons

    DEFF Research Database (Denmark)

    Brinkmann, Svend


    This paper argues the Wittgensteinian point that we can undo the psychologizing of psychology by conceiving of mental life as lived in the space of reasons. It is argued that mental life - human action, feeling and thinking - is constituted by normative connections and necessities rather than...... that it violates our conception of mental illness as something mental, yet outside the space of reasons...

  9. Mental health in Tamil cinema. (United States)

    Mangala, R; Thara, R


    Tamil cinema is a vibrant part of the lives of many in south India. A chequered history and a phenomenal growth have made this medium highly influential not only in Tamil Nadu politics, but also in the social lives of the viewers. This paper provides an overview of the growth of Tamil cinema, and discusses in detail the way mental health has been handled by Tamil films. Cinema can be used very effectively to improve awareness about mental health issues.

  10. Disability associated with mental disorders



    Background: Disability associated with mental illness is a major contributor to the global burden of disease. The present study looks at some aspects of disability associated with 7 psychiatric disorders: schizophrenia, bipolar affective disorder, anxiety disorders, depression, obsessive–compulsive disorder, dementia, and mental and behavioural disorders due to the use of alcohol. Aims: (i) To evaluate the nature and quantity of disabilities in the study groups; (ii) to compare the degree of ...

  11. The stigma of mental illness

    Directory of Open Access Journals (Sweden)

    Kordosi A


    Full Text Available Introduction:The stigma of mental illness is not a modern phenomenon, but it can now be approached scientifically. The stigma, because of the mental illness which characterizes a person, can be explained by the natural propensity of man to deliver biased and stereotyped estimates to phenomena he cannot explain, accept or face. Methodology:This study is an attempt to describe the concept of stigma and the impact of the stigma of mental illness in the personal and social life of the individual. The search for sources of this review was made through books on the topic and articles of the last twenty years, from online internet sources (pubmed, scopus, google scholar. Literature Review:Stigma brought about by illness from mental illness, is a complex process and concept, located in social interaction and the dynamics of social relations. The social stigma borne by mental illness in general, as well as the lack of information, ignorance, stereotypes, myths and prejudices, are the main reasons that characterize, even today, depression as a taboo subject. The stigma of mental illness is indeliblyimprinted in the identity of human suffering. In any case, the impact of stigma is critical for people who are sick. The psychological stress and difficult conditions that shape their daily lives aggravate their already compromised mental health, having a significant impact on the course and outcome of the disease itself. Key strategies to address stigma are protest, education and contact. Conclusions:A significant step in combating the stigma is to raise public awareness on the issues of mental health and their inclusion in society.

  12. [Mental health mainstreaming: promotion and recovery]. (United States)

    Chang, Chueh; Hsieh, Chia-Jung


    Mental health is a human right and fundamental to good personal health. Developing, planning, and implementing mental health programs is a key part of health policies worldwide. This paper uses the perspective of "mental health mainstreaming" to define mental health and explore its relationship with mental illness and psychiatric disease. Further, we apply this perspective to Taiwan's three-tiered community mental illness prevention strategy as a reference for mental health promotion and rehabilitation programs in hopes that all healthcare providers help facilitate holistic community health.

  13. Evolving society and mental health

    Directory of Open Access Journals (Sweden)

    Dipesh Bhagabati


    Full Text Available Numerous issues related to culture, occupation, gender, caste, and health, to name a few, have faced harshness of society from time immemorial. Reasons are debatable, ranging from somewhat understandable to completely unacceptable. There is no doubt that society is dynamic and it has changed its view on many of the issues with passing time. Mental health is one such issue which society has neglected for quite a long time. Even today, mental health and mentally ill people face stigma and discrimination in their family, society, and at their workplace. People do not feel comfortable talking about mental health, even if they know that there cannot be any health without a healthy mind. But, as Albert Einstein has said “learn from yesterday, live for today, and hope for tomorrow”, everything is not lost. The mentally ill patients who were once abandoned and left on their own have now started to get humane care and attention. This article discusses this very pertinent topic of changing society and mental health.

  14. Mental Retardation. Fact Sheet = El Retraso Mental. Hojas Informativas Sobre Discapacidades. (United States)

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This fact sheet on mental retardation is written in both English and Spanish. It begins with a vignette of a 15-year-old boy with mental retardation. Mental retardation is briefly explained as are some causes of mental retardation. It notes that a diagnosis of mental retardation looks at two things: first, the ability of a person's brain to learn,…

  15. Television and the promotion of mental health


    Milošević Ljiljana


    Current media campaigns, realized within national campaigns and actions on mental health prevention and promotion, are considered in this paper, in the context of expert public relation, as well as the whole society, towards mental health. Mental health promotion is determined as a range of activities by which individuals, community and society are being enabled to take control over mental health determinants and to improve it, but also as an action for improvement of mental health posi...

  16. Development of Mental Health Indicators in Korea


    Han, Hyeree; Ahn, Dong Hyun; Song, Jinhee; Hwang, Tae Yeon; Roh, Sungwon


    Objective: Promoting mental health and preventing mental health problems are important tasks for international organizations and nations. Such goals entail the establishment of active information networks and effective systems and indicators to assess the mental health of populations. This being said, there is a need in Korea develop ways to measure the state of mental health in Korea. Methods: This paper reviews the mental health indicator development policies and practices of seven organiza...

  17. Malaysia mental health country profile. (United States)

    Parameshvara Deva, M


    Malaysia is a tropical country in the heart of south east Asia with a population of 24 million people of diverse ethnic, cultural and religious backgrounds living in harmony in 330,000 km(2) of land on the Asian mainland and Borneo. Malaysia, which lies on the crossroads of trade between east and west Asia, has an ancient history as a centre of trading attracting commerce between Europe, west Asia, India and China. It has had influences from major powers that dominated the region throughout its history. Today the country, after independence in 1957, has embarked on an ambitious development project to make it a developed country by 2020. In this effort the economy has changed from one producing raw material to one manufacturing consumer goods and services and the colonial health system has been overhauled and social systems strengthened to provide better services for its people. The per capita income, which was under 1,000 US dollars at independence, has now passed 4,000 US dollars and continues to grow, with the economy largely based on strong exports that amount to over 100 billion US dollars. The mental health system that was based on institutional care in four mental hospitals at independence from British colonial rule in 1957 with no Malaysian psychiatrists is today largely based on over 30 general hospital psychiatric units spread throughout the country. With three local postgraduate training programmes in psychiatry and 12 undergraduate departments of psychiatry in the country--all started after independence--there is now a healthy development of mental health services. This is being supplemented by a newly established primary care mental health service that covers community mental health by integrating mental health into primary health care. Mental health care at the level of psychiatrists rests with about 140 psychiatrists most of whom had undertaken a four-year masters course in postgraduate psychiatry in Malaysia since 1973. However, there continues to be

  18. Mental Retardation and Parenting Stress

    Directory of Open Access Journals (Sweden)

    Eleni Siamaga


    Full Text Available Backround: The presence, upbringing and looking after of a mentally retarded child in the family, can become a threat to the mental health of its parents and is the main predisposing factor of stress for the parents.Aim: The purpose of this systematic review is (a to document the contemporary research bibliography related to the stress of parents with mentally retarded children, (b to aggregate the factors and secondary parameters based on the contemporary research related to the influence of the (child’s mental retardation on the parents and (c to show an intercultural aspect regarding the presence of stress to parents with mentally retarded children.Methods: Systematic review of research articles published in scientific journals included in the international academic databases HEAL-LING, SAGE, ELSEVIER, WILSON, SCIENCEDIRECT, MEDLINE, PUBMED, PsycINFO, Cochrane, EMBASE, SCIRUS and CINAHL having as search criteria and key words the terms («parental stress and mental retardation» [MeSH], «parenting stress and persons with special needs» [MeSH], «mental retardation and family problems» [MeSH], «stress and parents» [MeSH], «parenting and stress» [MeSH], «mental delay and parents» [MeSH], «developmental disabilities and family stress» [MeSH], «intellectual handicap and parenting» [MeSH], «maternal stress and child with disabilities» [MeSH].Discussion: The review has proven that all forms of mental retardation have an important -from a statistic point of viewimpacton the parents’ mental health. Anxiety, stress and depression are common symptoms mentioned by the parents.Additionally, there are individual variables such as the husband-wife relationship, the parents’ approach to their child’s disability, the parental strategies used in order to cope with the daily life of the child’s disability and the behavioural problems of their child, all of which contribute to the increase of the level of parental stress

  19. Programa de saúde mental Programme in mental health

    Directory of Open Access Journals (Sweden)

    Cid Guimarães


    Full Text Available É apresentado o programa de Saúde Mental decorrente de convênio estabelecido pela Secretaria da Saúde do Estado de São Paulo com a Universidade de São Paulo, através da Faculdade de Saúde Pública. Este convênio tem por finalidade a realização de estudos na área de Saúde Mental, tais como assistência psiquiátrica preventiva e pesquisas visando a medir transtornos mentais através de casos de óbito e na população da cidade e de cursos e atividades curriculares e extra-curriculares.The School of Public Health is conducting a project, sponsored by the Health Department of the State of S. Paulo Government, aiming at: studying the integration of a team of mental health workers in a polivalent community health center; carrying out two large surveys on the incidence and prevalence of mental disorders and some of their characteristics; promoting courses and seminars on Mental Health for the personnel of Community Health Centers.

  20. Nutritional therapies for mental disorders. (United States)

    Lakhan, Shaheen E; Vieira, Karen F


    According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who

  1. Nutritional therapies for mental disorders

    Directory of Open Access Journals (Sweden)

    Vieira Karen F


    Full Text Available Abstract According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD, addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD. Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such

  2. Mental Illness And Brain Disease. (United States)

    Bedrick, Jeffrey D


    It has become common to say psychiatric illnesses are brain diseases. This reflects a conception of the mental as being biologically based, though it is also thought that thinking of psychiatric illness this way will reduce the stigma attached to psychiatric illness. If psychiatric illnesses are brain diseases, however, it is not clear why psychiatry should not collapse into neurology, and some argue for this course. Others try to maintain a distinction by saying that neurology deals with abnormalities of neural structure while psychiatry deals with specific abnormalities of neural functioning. It is not clear that neurologists would accept this division, nor that they should. I argue that if we take seriously the notion that psychiatric illnesses are mental illnesses we can draw a more defensible boundary between psychiatry and neurology. As mental illnesses, psychiatric illnesses must have symptoms that affect our mental capacities and that the sufferer is capable of being aware of, even if they are not always self-consciously aware of them. Neurological illnesses, such as stroke or multiple sclerosis, may be diagnosed even if they are silent, just as the person may not be aware of having high blood pressure or may suffer a silent myocardial infarction. It does not make sense to speak of panic disorder if the person has never had a panic attack, however, or of bipolar disorder in the absence of mood swings. This does not mean psychiatric illnesses are not biologically based. Mental illnesses are illnesses of persons, whereas other illnesses are illnesses of biological individuals.

  3. Copenhagen infant mental health project

    DEFF Research Database (Denmark)

    Væver, Mette Skovgaard; Smith-Nielsen, Johanne; Lange, Theis


    such as physical and mental health, educational and labor market success, social network and establishing of family. Secure attachment is associated with optimal outcomes in all developmental domains in childhood, and both insecure and disorganized attachment are associated with a range of later problems......Background: Infant mental health is a significant public health issue as early adversity and exposure to early childhood stress are significant risk factors that may have detrimental long-term developmental consequences for the affected children. Negative outcomes are seen on a range of areas...... in the City of Copenhagen, Denmark. During the project a general population of an estimated 17.600 families with an infant aged 2–12 months are screened for two known infant mental health risks, maternal postnatal depression and infant social withdrawal. Eligible families (N = 314), who agree to participate...

  4. Leadership and mental health nursing. (United States)

    Cleary, Michelle; Horsfall, Jan; Deacon, Maureen; Jackson, Debra


    This discussion paper argues for the critical importance of successful leadership for effective mental health nursing, observing that nursing leadership has long been regarded problematically by the profession. Using empirical and theoretical evidence we debate what leadership styles and strategies are most likely to result in effective, recovery-orientated mental health nursing. Models of transformational and distributed leadership are found to be highly congruent with mental health nursing values, yet the literature suggests it is a type of leadership more often desired than experienced. We note how the scholarly literature tends to ignore the "elephant in the room" that is organizational power, and we question whether transformational leadership pursued within a specific clinical context can influence beyond those confines. Nevertheless it is within these contexts that consumers experience nursing, effective or otherwise, thus we should advocate what is known about effective leadership wherever it is required.

  5. 21.4.Mental deficiency

    Institute of Scientific and Technical Information of China (English)


    930413 Clinlcal study of mental disorders inpost—stroke patients.WANG Huanlin (王焕林),et al.102nd Hosp,PLA Changzhou,213003.Chin J Nerv & Ment Dis 1992;18(5):281—283.The mental disorder has been studied bymeans of DSM-Ⅱ diagnostic criteria in 104hospitalized stroke patients.The results re-vealed that the prevalence of mental disorderwas 46.2% in post-stroke patients.Theprevalence of poststroke depression (PSD),de-pressive neurosis (DN),multiple infarct demen-tia (MID),and post—stroke mania (PSM) were22.1%,11.5%,8.7%,and 3(?)8% respectively.It was indicated that the lesions of frontal cortexand left basal ganglia were strongly associated

  6. Mental models and user training

    Directory of Open Access Journals (Sweden)

    Saša Zupanič


    Full Text Available One of the functions of the reference service is user training which means teaching users how to use the library and it's information sorces (nowadays mainly computerized systems. While the scientific understanding of teaching/learning process is shifting, changes also affect the methods of user training in libraries.Human-computer interaction (HCI is an interdisciplinary and a very active research area which studies how humans use computers - their mental and behavioral characteristics. The application of psychological theories to HCI are especially great on three areas: psychological (mental, conceptual models, individual differences, and error behavior.The mental models theory is powerful tool for understanding the ways in which users interact with an information system. Claims, based on this theory can affect the methods (conceptualization of user training and the overall design of information systems.

  7. Copenhagen infant mental health project:

    DEFF Research Database (Denmark)

    Væver, Mette Skovgaard; Smith-Nielsen, Johanne; Lange, Theis


    Background: Infant mental health is a significant public health issue as early adversity and exposure to early childhood stress are significant risk factors that may have detrimental long-term developmental consequences for the affected children. Negative outcomes are seen on a range of areas...... such as physical and mental health, educational and labor market success, social network and establishing of family. Secure attachment is associated with optimal outcomes in all developmental domains in childhood, and both insecure and disorganized attachment are associated with a range of later problems...... in the City of Copenhagen, Denmark. During the project a general population of an estimated 17.600 families with an infant aged 2–12 months are screened for two known infant mental health risks, maternal postnatal depression and infant social withdrawal. Eligible families (N = 314), who agree to participate...

  8. Mental depression and kundalini yoga. (United States)

    Devi, S K; Chansauria, J P; Udupa, K N


    In cases of mental depression, the plasma serotonin, melatonin and glutamate levels are increased along with the lowering of urinary - 5 - hydroxyindole acetic acid, plasma monoamine oxidase and cortisol levels following three and six months Practice of Kundalini Yoga. The pulse rate and blood pressure in these patients are also lowered after Kundalini Yoga practice. Thus, the practice of Kundalini Yoga helps to maintain a perfect homeostasis by bringing an equilibrium between the sympathetic and parasympathetic activities and it can be used as a non - medical measure in treating patients with mental depression.

  9. Malayalam cinema and mental health. (United States)

    Menon, Koravangattu Valsraj; Ranjith, Gopinath


    There is a tradition of using films to teach various aspects of psychiatry and we feel that Malayalam cinema can also be used suitably to teach effectively. These films can be an invaluable resource in cultural competency training as they depict the effects of culture on psychopathology and cultural and regional influences on attitudes to mental illness and stigma. We also note that the portrayal is often far from reality but this is not a barrier for using the films as an effective alternative to traditional and didactic teaching methods. This method of teaching can stimulate interest and discussion and demystify the myths of novice students and others about mental health.

  10. Medio laboral y salud mental.

    Directory of Open Access Journals (Sweden)

    Alberto Fernández Liria


    Full Text Available Se revisan las formas predominantes de experimentar el trabajo y el medio laboral en el mundo occidental desde la revolución industrial analizando el surgimiento de diferentes funciones, como: medio de subsistencia, generador de derechos, jerarquizador en el entramado social, fuente de significado personal y entorno privilegiado de relaciones interpersonales significativas. Se discute el papel que la actividad productiva puede tener en el sistema de significados que configura a los individuos como miembros de una sociedad concreta, y, por tanto, en su salud mental. En base a ello se discute el papel del sistema de atención la salud mental en este terreno.

  11. Auto cannibalism in mental retardation

    Directory of Open Access Journals (Sweden)

    Rohit Verma


    Full Text Available Mental retardation (MR deems an individual more vulnerable to psychopathologies. The individual may develop an array of behavioral disturbances manifesting themselves in the form of aggressive and destructive conduct, violent fits of anger, stereotyped, or self-injuring behavior. Self-injurious behavior is heterogeneous in nature ranging from mild to severe variant. We report a case of a 7-year-old boy with MR with self-inflicted severe oral injuries of cannibalistic nature presenting as cleft lip and palate. A more extensive research is needed on the problem behaviors in mentally retarded patients for early detection and effective and timely intervention leading to a better outcome.

  12. A study of mental models

    Directory of Open Access Journals (Sweden)

    A. Tarciso Borges


    Full Text Available The concept of mental models is being used in several areas of knowledge in order to study the representations users have about physical systems and events, as well as the content of such representations. However, it cannot be considered a unitary concept. This paper discusses the assumptions envolved in different areas of knowledge and describes a study of the mental model of magnetism held by students and professionals such as electricians physics teachers, and engineers. The identified model stress two aspects: what is the origin of permanent magnets and what is the mechanism of the magnetic interaction.

  13. Mild mental stress in diabetes

    DEFF Research Database (Denmark)

    Hildebrandt, P; Mehlsen, J; Sestoft, L;


    A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements......--increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics....

  14. Stigma and Mental Illness: Investigating Attitudes of Mental Health and Non-Mental-Health Professionals and Trainees (United States)

    Smith, Allison L.; Cashwell, Craig S.


    The authors explored attitudes toward adults with mental illness. Results suggest that mental health trainees and professionals had less stigmatizing attitudes than did non-mental-health trainees and professionals. Professionals receiving supervision had higher mean scores on the Benevolence subscale than did professionals who were not receiving…

  15. Mental EEG Analysis Based on Infomax Algorithm

    Institute of Scientific and Technical Information of China (English)

    WUXiao-pei; GuoXiao-jing; ZANGDao-xin; SHENQian


    The patterns of EEG will change with mental tasks performed by the subject. In the field of EEG signal analysis and application, the study to get the patterns of mental EEG and then to use them to classify mental tasks has the significant scientific meaning and great application value. But for the reasons of different artifacts existing in EEG, the pattern detection of EEG under normal mental states is a very difficult problem. In this paper, Independent Component Analysisis applied to EEG signals collected from performing different mental tasks. The experiment results show that when one subject performs a single mental task in different trials, the independent components of EEG are very similar. It means that the independent components can be used as the mental EEG patterns to classify the different mental tasks.

  16. Boletín Salud Mental




    Boletín informativo de los profesionales de la Red de Salud Mental del Servicio de Salud del Principado de Asturias Newsletter for professionals in the mental health network Asturias Servicio de Salud del Principado de Asturias

  17. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility (United States)

    ... after the methamphetamine exposure, and obtained magnetic resonance images (MRI) of the brain before and after the exposure. Figure 1. Reversal Trial Studies the Impact of Methamphetamine on Monkeys’ Mental Flexibility The trial evaluates an animal’s mental ...

  18. Plastic Surgeons Often Miss Patients' Mental Disorders (United States)

    ... More Health News on: Mental Disorders Plastic and Cosmetic Surgery Recent Health News Related MedlinePlus Health Topics Mental Disorders Plastic and Cosmetic Surgery About MedlinePlus Site Map FAQs Customer Support Get ...

  19. Mental Health: Keeping Your Emotional Health (United States)

    ... Basics Sports Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth ... Basics Sports Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth ...

  20. Mental Health May Affect Chances Against Cancer (United States)

    ... page: Mental Health May Affect Chances Against Cancer Early research suggests ... Our findings contribute to the evidence that poor mental health might have some predictive capacity for certain physical ...

  1. Mental Health: What's Normal, What's Not? (United States)

    Healthy Lifestyle Adult health Understanding what's considered normal mental health can be tricky. See how feelings, thoughts and behaviors determine mental health and how to recognize if you or a ...

  2. [Are Mental Disorders Natural Kinds?]. (United States)

    Flórez Quintero, Daian Tatiana


    A problem for both philosophers of Psychiatry and Psychiatrists within the domain of nosology is to determine which could be the more appropriate model to classify mental illnesses. Such an endeavor also requires questioning the very nature of mental illness. While trying to cope with the philosophical challenges of such a task, Peter Zachar purports to show that the nosological work in Psychiatry should not adhere to the model of natural kinds. He even considers that it is mistaken to treat mental disorders as natural kinds. Nonetheless, Zachar's view on the existence of natural kinds-even in domains where there is little room for doubting about their existence, like Chemistry-is very unstable. In 2001 he holds that there are no natural kinds, but in 2008 he argues that his objections to the model of natural kinds are more the manifestation of his skepticism against a tradition. Although the problem of the existence of natural kinds shall not be dealt with in this article, a brief description on how deflated is Zachar's view on this matter in 2008 is presented, with the central part of the article devoted to reconstruct and examine his rationale for the thesis that mental disorders are not natural kinds. In the critical section of this paper, it is suggested that, although Zachar's thesis may be right, the arguments he gives to support it are quite flawed.

  3. Barometer. Mental health January 2005. (United States)


    Mental health trust chief executives are increasingly confident about recruiting crisis resolution and early intervention teams, according to the new HSJ Barometer survey. However, very few expect to gain foundation status in the next two years. The survey also shows that bed occupancy rates are increasing, with about a fifth of trusts showing rates above 100 per cent.

  4. Detection of Malingered Mental Retardation (United States)

    Shandera, Anne L.; Berry, David T. R.; Clark, Jessica A.; Schipper, Lindsey J.; Graue, Lili O.; Harp, Jordan P.


    In a cross-validation of results from L. O. Graue et al. (2007), standard psychological assessment instruments, as well as tests of neurocognitive and psychiatric feigning, were administered under standard instructions to 24 participants diagnosed with mild mental retardation (MR) and 10 demographically matched community volunteers (CVH). A 2nd…

  5. Mental fatigue impairs emotion regulation. (United States)

    Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique


    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.

  6. Issues in consumer mental health information.


    Angier, J J


    Consumer health information as applied to mental health includes areas such as the diagnosis, management, and treatment of mental illness, as well as self-help, emotional wellness, and the relationship between life events, stress, and disease. This paper presents issues specific to the provision of mental health information to the layperson, e.g., confidentiality, literacy, competence, the social stigma of mental illness, the state of the art in psychiatry, popular psychology, and treatment f...

  7. Violence and mental illness: an overview


    Stuart, Heather


    This paper evaluates the relationship of mental illness and violence by asking three questions: Are the mentally ill violent? Are the mentally ill at increased risk of violence? Are the public at risk? Mental disorders are neither necessary nor sufficient causes of violence. Major determinants of violence continue to be socio-demographic and economic factors. Substance abuse is a major determinant of violence and this is true whether it occurs in the context of a concurrent ...

  8. DocSaludMental en netvibes


    Onís, Ricardo


    DocSaludMental es un escritorio virtual que, a partir de la plataforma netvibes, permite el acceso a información especializada y actualizada mediante la sindicación de contenidos a todos los profesionales de la red de salud mental en el Principado de Asturias DocSaludMental is a virtual desktop that allows access to expert information and updated from content syndication to all professionals in the mental health network in the Principality of Asturias

  9. Mental Health Service Delivery Systems and Perceived Qualifications of Mental Health Service Providers in School Settings (United States)

    Dixon, Decia Nicole


    Latest research on the mental health status of children indicates that schools are key providers of mental health services (U.S. Department of Health and Human Services, 2003). The push for school mental health services has only increased as stakeholders have begun to recognize the significance of sound mental health as an essential part of…

  10. States Pass Diverse Slate of Mental Health Legislation in 2013. Mental Health: 2013 Legislative Session (United States)

    Thomsen, Jennifer


    Recent violence in schools and on college campuses has brought into sharp focus the need to address mental health issues in educational settings. Getting students with mental health problems the help they need, without stigmatizing mental illness, may help prevent future tragedies. Children with mental health problems face a host of challenges,…

  11. The Role of Bilingual Workers without Professional Mental Health Training in Mental Health Services for Refugees. (United States)

    Egli, Eric

    This paper discusses the use of bilingual workers who do not have formal mental health training as mediators and providers of mental health care for refugees. The introduction provides a background discussion of the need for refugee mental health services, the characteristics of bilingual mental health workers, and the work places and expectations…

  12. Defendants with Intellectual Disabilities and Mental Health Diagnoses: Faring in a Mental Health Court (United States)

    Burke, M. M.; Griggs, M.; Dykens, E. M.; Hodapp, R. M.


    Background: Begun in the late 1990s, mental health courts are specialty criminal courts developed to address the needs of persons with mental illness. Methods: As many persons with intellectual disabilities (IDs) may overlap in the mental health court system, we used mental health court records to examine the phenomenology and outcomes of 224…

  13. Mental health in China: current status and prevention and control of mental disorders

    Institute of Scientific and Technical Information of China (English)



    @@ Mental health is the balance between all aspects of life (e.g. social, physical, spiritual and emotional). Mental health is far more than absence of mental illness and has to do with the prevention and management of various kinds of psychoses and psychological and behavior disorders so as to improve overall level of mental health in populations.

  14. Special Considerations When Providing Mental Health Services for Persons with Mental Retardation. (United States)

    Schoen, Jill F.

    Unique challenges surface when providing services in community mental health centers for persons with mental retardation and mental illness. Before any type of mental health treatment for a client with this dual diagnosis can begin, proper assessment is critical. Clinicians working with this population have to adapt their treatment strategies and…

  15. Mental Maps and Metaphors in Academic Libraries. (United States)

    McInnis, Raymond G.


    Discusses the concept of mental (or cognitive) maps--the images we construct in our minds to help us understand something--and argues that geographers' literature on mental maps can provide greater understanding of scientific literature's formats, conventions, processes, and formulations. Three classes of perception studies for mental maps are…

  16. Cannabis Use and Mental Health Problems

    NARCIS (Netherlands)

    van Ours, J.C.; Williams, J.


    This paper investigates whether cannabis use leads to worse mental health. To do so, we account for common unobserved factors affecting mental health and cannabis consumption by modeling mental health jointly with the dynamics of cannabis use. Our main finding is that using cannabis increases the li

  17. Prejudice, Mental Health and Family Life. (United States)

    Ackerman, Nathan W.

    This pamphlet explores the relationship among prejudice, mental health, and family life. Prejudice is learned behavior, initially within the family unit which sets the framework for good or bad mental health as well as for the development of positive or negative attitudes. The family also determines the degree and kind of mental health of each…




  19. Mental Images towards the Concept of Drama (United States)

    Pekdogan, Serpil; Korkmaz, Halil Ibrahim


    The aim of this study is to examine the mental images of preschool teacher candidates related to the concept of drama via metaphors. We questioned these questions; "What are the metaphors or mental images of teacher candidates?," "Under which conceptual categories are these metaphors or mental images can be collected?" and…

  20. Positive mental health: is there a cross-cultural definition? (United States)

    Vaillant, George E


    SEVEN MODELS FOR CONCEPTUALIZING POSITIVE MENTAL HEALTH ARE REVIEWED: mental health as above normal, epitomized by a DSM-IV's Global Assessment of Functioning (GAF) score of over 80; mental health as the presence of multiple human strengths rather than the absence of weaknesses; mental health conceptualized as maturity; mental health as the dominance of positive emotions; mental health as high socio-emotional intelligence; mental health as subjective well-being; mental health as resilience. Safeguards for the study of mental health are suggested, including the need to define mental health in terms that are culturally sensitive and inclusive, and the need to empirically and longitudinally validate criteria for mental health.

  1. Mental Health in Developing Countries: Challenges and Opportunities in Introducing Western Mental Health System in Uganda



    Background: Despite decades of disagreement among mental health practitioners and researchers in the Western world pertaining to the causation, classification and treatment of mental disorders there is an ongoing push to implement western mental health models in developing countries. Little information exists on the adaptability of western mental health models in developing countries. Method: This paper presents a review of the attempt to implement a western-oriented mental health system ...

  2. Mental health among students of pedagogical universities

    Directory of Open Access Journals (Sweden)

    Malinauskas R.


    Full Text Available This article deals with questions of mental health among students of pedagogical universities. There were analysed differences in the level of mental health among sporting and non-sporting students. Two methods were used in the inquiry. Stepanov's questionnaire was used to estimate the level of mental health, Gundarov's questionnaire was used to evaluate psychical satisfaction. The sample consisted of 263 sporting students (athletes and 288 non-sporting students. Results have shown that the level of mental health among sporting students was higher than the level of mental health among non-sporting students.

  3. The Role of Empathy in Mental Attribution

    Directory of Open Access Journals (Sweden)

    Brunsteins, Patricia


    Full Text Available This work examines in what extent a notion of empathy may clarify mindreading’s debate. Taking into account an interdisciplinary and integrative notion of empathy, compatibility with mental attribution strategies both mental simulation and theory-theory, in non pure versions, is evaluated. Firstly, new empirical research is supposed to contribute strengthening an integrative empathy instead of theory-theory or mental simulation `s points of view. Secondly, new empirical research will bring better tools to distinguish between empathy and simulation. Consequently, the relationship between empathy and mental attribution theories may be better delimited and a full mental attribution theory may possibly be proposed.

  4. Rural mental health: neither romanticism nor despair. (United States)

    Wainer, J; Chesters, J


    This paper explores the relationship between rural places and mental health. It begins with a definition of mental health and an outline of the data that have led to the current concern with promoting positive mental health. We then consider aspects of rural life and place that contribute to positive mental health or increase the likelihood of mental health problems. Issues identified include environment, place, gender identity, violence and dispossession and the influence of the effects of structural changes in rural communities. The paper concludes with a discussion of some of the determinants of resilience in rural places, including social connectedness, valuing diversity and economic participation.

  5. Why focus on mental health systems?

    Directory of Open Access Journals (Sweden)

    Minas Harry


    Full Text Available Abstract The global situation for people with mental illness – in developing and developed countries – is dire. Legislative and human rights protections are frequently lacking. Mental health budgets are inadequate. There are insufficient numbers of skilled policy makers, managers and clinicians. Communities are poorly informed about mental health and illness and not well organised for purposes of advocacy. In most of the world, mental health services are inaccessible or of poor quality. Most people who would benefit from psychiatric treatment and rehabilitation do not have affordable access to such services. Leadership – at all levels – for mental health system development needs to be greatly strengthened. While mental health research attention and funds are devoted predominantly to neuroscience and clinical research, we believe that the highest global mental health research priority is mental health systems research. There is an urgent need to focus on the development of effective, appropriate, affordable mental health services. The evidence base for such development is currently weak. The International Journal of Mental Health Systems aims to stimulate greater attention to the central importance of building functioning mental health systems. Rapid publication and global reach through open access will make this journal a resource for all those who wish to contribute to such development.

  6. Public perception of mental health in Iraq

    Directory of Open Access Journals (Sweden)

    Al-Hasoon Saad


    Full Text Available Abstract Background People who suffer from mental illness, the professionals who treat them, and indeed the actual concept of mental illness are all stigmatised in public perception and often receive very negative publicity. This paper looks at Iraq, which has a population of 30 million who are mainly Moslem. Mental health services and professionals have historically been sparse in Iraq with 1 psychiatrist per 300,000 before 2003 falling to 1 per million until recently and 1 primary care centre (40 Healthcare Workers including 4 General Practitioners to 35,000 population, compared with 1 GP per 1700 population in the UK. Methods We aimed to assess public attitudes and perceptions to mental illness. Participants were asked to complete a questionnaire (additional file 1, which was designed specifically for Iraqi contexts and was made available in 2 languages. The survey was carried out in 500 participants' homes across 2 districts of Baghdad. Additional file 1 Public Perception of Mental Illness Questionnaire. Click here for file Results The response rate of the survey was 86.4%. The paper shows respondents views on the aetiology of mental illness, perceptions of people with mental illness and attitudes towards care and treatment of people with mental illness. Conclusions This survey of public attitudes towards mental illness in Iraq has shown that community opinion about the aetiology of mental illness is broadly compatible with scientific evidence, but understanding of the nature of mental illness, its implications for social participation and management remains negative in general.

  7. Causal reasoning with mental models. (United States)

    Khemlani, Sangeet S; Barbey, Aron K; Johnson-Laird, Philip N


    This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex.

  8. Causal reasoning with mental models

    Directory of Open Access Journals (Sweden)

    Sangeet eKhemlani


    Full Text Available This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex.

  9. Mental fatigue: costs and benefits. (United States)

    Boksem, Maarten A S; Tops, Mattie


    A framework for mental fatigue is proposed, that involves an integrated evaluation of both expected rewards and energetical costs associated with continued performance. Adequate evaluation of predicted rewards and potential risks of actions is essential for successful adaptive behaviour. However, while both rewards and punishments can motivate to engage in activities, both types of motivated behaviour are associated with energetical costs. We will review findings that suggest that the nucleus accumbens, orbitofrontal cortex, amygdala, insula and anterior cingulate cortex are involved evaluating both the potential rewards associated with performing a task, as well as assessing the energetical demands involved in task performance. Behaviour will only proceed if this evaluation turns out favourably towards spending (additional) energy. We propose that this evaluation of predicted rewards and energetical costs is central to the phenomenon of mental fatigue: people will no longer be motivated to engage in task performance when energetical costs are perceived to outweigh predicted rewards.

  10. Hinduism, marriage and mental illness. (United States)

    Sharma, Indira; Pandit, Balram; Pathak, Abhishek; Sharma, Reet


    For Hindus, marriage is a sacrosanct union. It is also an important social institution. Marriages in India are between two families, rather two individuals, arranged marriages and dowry are customary. The society as well as the Indian legislation attempt to protect marriage. Indian society is predominantly patriarchal. There are stringent gender roles, with women having a passive role and husband an active dominating role. Marriage and motherhood are the primary status roles for women. When afflicted mental illness married women are discriminated against married men. In the setting of mental illness many of the social values take their ugly forms in the form of domestic violence, dowry harassment, abuse of dowry law, dowry death, separation, and divorce. Societal norms are powerful and often override the legislative provisions in real life situations.

  11. The 2013 Canadian Forces Mental Health Survey (United States)

    Bennett, Rachel E.; Boulos, David; Garber, Bryan G.; Jetly, Rakesh; Sareen, Jitender


    Objective: The 2013 Canadian Forces Mental Health Survey (CFMHS) collected detailed information on mental health problems, their impacts, occupational and nonoccupational determinants of mental health, and the use of mental health services from a random sample of 8200 serving personnel. The objective of this article is to provide a firm scientific foundation for understanding and interpreting the CFMHS findings. Methods: This narrative review first provides a snapshot of the Canadian Armed Forces (CAF), focusing on 2 key determinants of mental health: the deployment of more than 40,000 personnel in support of the mission in Afghanistan and the extensive renewal of the CAF mental health system. The findings of recent population-based CAF mental health research are reviewed, with a focus on findings from the very similar mental health survey done in 2002. Finally, key aspects of the methods of the 2013 CFMHS are presented. Results: The findings of 20 peer-reviewed publications using the 2002 mental health survey data are reviewed, along with those of 25 publications from other major CAF mental health research projects executed over the past decade. Conclusions: More than a decade of population-based mental health research in the CAF has provided a detailed picture of its mental health and use of mental health services. This knowledge base and the homology of the 2013 survey with the 2002 CAF survey and general population surveys in 2002 and 2012 will provide an unusual opportunity to use the CFMHS to situate mental health in the CAF in a historical and societal perspective. PMID:27270738



    Devi, Sanjenbam Kunjeshwori; Chansauria, J. P. N.; Udupa, K. N.


    In cases of mental depression, the plasma serotonin, melatonin and glutamate levels are increased along with the lowering of urinary – 5 – hydroxyindole acetic acid, plasma monoamine oxidase and cortisol levels following three and six months Practice of Kundalini Yoga. The pulse rate and blood pressure in these patients are also lowered after Kundalini Yoga practice. Thus, the practice of Kundalini Yoga helps to maintain a perfect homeostasis by bringing an equilibrium between the sympathetic...

  13. [Mental capacity of psychiatric patients]. (United States)

    Wu, Kevin Chien-Chang


    Nearly every society maintains legal norms that define those members of society qualified to participate in social affairs. Mental capacity and legal competence are deemed necessary conditions for legal actions to have legal validity. On Nov. 23, 2009, newly revised adult guardianship provisions came into effect in Taiwan. However, there has been lack of discussion with regard to how assessments of mental capacity and legal competence should be conducted on psychiatric patients. This paper reviewed relevant overseas literature on this subject and followed common practice in separating legal mental capacity into causal and functional components. The causal component predicates the diseases and illnesses that render the disability, while the functional component represents legally substantial impairments in terms of cognition, emotion and behavior. The paper explored functional component contents, including finance management, individual health care, independence in daily life, interpersonal relationships and communing. Findings pointed out that in setting up competence standards, a trade-off between respect for autonomy and beneficence is unavoidable. As Taiwan does not have rich empirical data on competence assessments and decisions, collaboration between the legal and psychiatric professions is recommended to engage in relevant research to enhance legal consistencies and the science of competence assessment.

  14. Mental Illness and Mental Health Defenses: Perceptions of the Criminal Bar. (United States)

    Frierson, Richard L; Boyd, Mary S; Harper, Angela


    As the number of state mental hospital beds declines, persons with persistent mental illness are increasingly encountered by those working in the legal system. Attorneys may have little experience in working with this population. This research involved a 32-item written survey of the 492 members of the criminal bar in South Carolina. Demographic variables were surveyed, and attorneys were asked to define two common terms describing mental illnesses (delusion and psychosis) and the legal criteria for verdicts of not guilty by reason of insanity and guilty but mentally ill. They were also asked to identify the most severe mental illness (schizophrenia). Attitudes about these verdicts and about working with defendants who are mentally ill were also surveyed. Results indicate that attorneys are fairly knowledgeable about mental illness, but not verdicts involving mental illness, particularly the verdict of guilty but mentally ill. Most attorneys prefer to work with clients who do not have mental illness. However, as they become more experienced interacting with defendants who are affected by mental illness, they become more knowledgeable and are more willing to defend them. A large majority believe that their law school education about mental illness was inadequate. When comparing attorney occupations, public defenders were the most knowledgeable about mental illness and mental health defenses, followed by prosecutors and private defense attorneys. Judges were the least knowledgeable group.

  15. [Perioperative disorders of mental functions]. (United States)

    Tonković, Dinko; Adam, Visnja Nesek; Kovacević, Marko; Bogović, Tajana Zah; Drvar, Zeljko; Baronica, Robert


    Mental disorders are characterized by disturbances of thought, perception, affect and behavior, which occur as a result of brain damage. Recognizing and treating these conditions is necessary not only for psychiatrists but for all physicians. Disorder of mental function is one of the most common associated conditions in intensive care unit (ICU) patients. However, disturbances of mental function often remain unrecognized. In ICU patients, different types of mental function disorders may develop. They range from sleep disorders, severe depression, anxiety, posttraumatic stress disorder (PTSD) to cognitive disorders including delirium. The causes of mental dysfunction in ICU patients can be divided into environmental and medical. Cognitive disorders are related to mental processes such as learning ability, memory, perception and problem solving. Cognitive disorders are usually not prominent in the early postoperative period and in many cases are discovered after hospital discharge because of difficulties in performing everyday activities at home or at work. The etiology of postoperative cognitive impairment is unclear. Older age, previous presence of cognitive dysfunction, severity of disease, and polypharmacy with more than four drugs are some of the risk factors identified. Delirium is a multifactorial disorder. It is an acute confusional state characterized by alteration of consciousness with reduced ability to focus, sustain, or shift attention. It is considered as the most common form of mental distress in ICU patients. Nearly 30% of all hospitalized patients pass through deliriant phase during their hospital stay. Delirium can last for several days to several weeks. Almost always it ends with complete withdrawal of psychopathological symptoms. Sometimes it can evolve into a chronic brain syndrome (dementia). The causes are often multifactorial and require a number of measures to ease the symptoms. Delirious patient is at risk of complications of immobility and

  16. Attitudes of psychiatry residents toward mental illness

    Directory of Open Access Journals (Sweden)

    Pejović-Milovančević Milica


    Full Text Available Introduction. Attitudes of lay people and physicians towards mentally ill patients are frequently highly biased. The aim of this study was to investigate differences in attitudes of psychiatry and internal medicine residents toward mental illness and to establish the relationship between their attitudes and their personal characteristics. Material and methods. The sample consisted of 45 psychiatry and 36 internal medicine residents. The attitudes toward mental illness were assessed using Opinions about Mental Illness Questionnaire (OMI and personality traits were examined using the Eysenck Personality Questionnaire (EPQ. Results. Our findings showed that in regard to internal medicine residents, psychiatry residents do not consider mentally ill patients to be inferior and dangerous. Psychiatry residents have a benevolent attitude toward the mentally ill. Personality traits of psychiatry residents were not related to their opinions about mental illness. Discussion. The results suggest that there is a need to develop strategies that would bring about changes in the curriculum of training programs for medical residents, including proper training in mental health issues. Such strategies should help in destigmatization of persons with mental disorders and increase the competence of physicians to deal with mentally ill. .

  17. Nudos mentales : Salud mental : Una introducción


    Ingeberg, Mette Holme; Grudt, Solveig Kirsti


    Boken er primært rettet mot studenter innenfor områdene helse- og sosialfag. Den vil også være nyttig for mennesker med psykiske problemer og deres pårørende, og for helsepersonell for øvrig. Et viktig mål med denne boken har vært å gjøre egne erfaringer og kompetanse på området psykisk helse tilgjengelig for helsepersonell i Nicaragua. Mye av boken er basert på boken Mentale knagger, skrevet av Mette Holme Ingeberg, Dag-Willy Tallaksen og Børge Eide i 2006.

  18. Congenital Insensitivity to Pain with Anhidrosis (CIPA Manifested with Chronic Osteomyelitis; A Case Report

    Directory of Open Access Journals (Sweden)

    Fatih Kucukdurmaz


    Full Text Available      Chronic osteomyelitis is a very rare entity among children. Also congenital insensitivity to pain with anhidrosis (CIPA is a very rare autosomal-recessive disease  of the nervous system which is one of the hereditary sensory and autonomic neuropathies (HSAN. Loss of pain, fever due to anhidrosis, recurrent fractures, chronic osteomyelitis, mental retardation, self mutilation, wound ulcers can be seen. We present a 10-year-old boy with loss of generalized pain sensation, chronic osteomyelitis on his right distal femur, bilateral corneal opacities, and decreased mental capacity.

  19. From Mental Health to Mental Wealth in Athletes: Looking Back and Moving Forward. (United States)

    Uphill, Mark; Sly, Dan; Swain, Jon


    Considerations of athletes' mental health are typically framed in the language of mental illness (Hughes and Leavey, 2012), a situation that contributes to stigmatization, denial, and the prevention of effective care. In this article, we provide a critical, narrative review of the extant literature on athlete mental health. Specifically, we begin by providing a brief synopsis of the extant literature on athletes' mental health, illustrating both what we know about (i) the prevalence of mental health issues in sport and (ii) variables contributing to help-seeking behaviors in athletes. Against, this backdrop, we outline Keyes' (2002) two-continuum model of mental health as a theoretical framework that has considerable promise in understanding, talking-about, and intervening to enhance, athletes' mental health. This model posits two related, but distinct dimensions: one continuum indicates the presence or absence of mental health, the other the presence or absence of mental illness. From this perspective, a number of possibilities emerge. For instance, athletes could simultaneously have both positive mental health and experience of mental illness. Alternatively, athletes could be free from mental illness, but in Keyes' terms be "languishing" (i.e., experiencing low levels of mental health). Implications for interventions based on the two-continuum model are discussed, particularly drawing on assets-based approaches to enhance flourishing (Theokas et al., 2005). We conclude the review by considering limitations in our understanding of how to promote flourishing and suggest avenues for further research.

  20. Mental and Medical sciences today

    Directory of Open Access Journals (Sweden)

    David L. Rowland


    Full Text Available Journal of Mind and Medical Sciences is designed as a free online, open access, interdisciplinary and peer-reviewed journal. The JMMS mission is to address ideas and issues related to mind and medicine, publishing scientific review and empirical papers regarding mental and medical health and disease. Our goal is to stimulate constructive debates among scholars, researchers, physicians, scientists and health professionals with respect to the latest discoveries and trends in the field. The journal pays special attention to interdisciplinary and integrative perspectives, focusing primarily on papers approaching mind and body as a unitary domain of study. Our supposition is that the study of the human body and mind needs to be better integrated—in fact should not be studied in isolation from one another, a position that originates fact from the collaborative efforts of the two main editors, namely a psychologist and a physician. As an example, the mind body problem—an age-old question—is still a much debated topic. Despite enormous progress in neuroimaging, it remains unclear how abstract ideas come to “control” the physical brain and body to generate actions, responses, and behaviors. Thus, abstract ideas of the mind (e.g., the desire to seek a promotion, to become famous, or to help those surrounding you can drive decision making and life choices more strongly than the concrete/ biological needs of the body (food, warmth, shelter, etc.. From a pathological perspective, heavy psychological and physical burden can “overload” the mind, creating a mental condition of stress which may then negatively impact bodily function through symptoms such as gastric ulcer, hypertension, and so on. From the opposite perspective, the body and brain can interfere with and direct the functioning of mind. The need for sleep, for example, is due to fluctuation of neuromodulators within the brain. When such neuromodulators are pharmacologically manipulated

  1. Neurophysiological Correlates of Various Mental Perspectives

    Directory of Open Access Journals (Sweden)

    Thilo eHinterberger


    Full Text Available A common view of consciousness is that our mind presents emotions, experiences and images in an internal mental (re-presentation space which in a state of wakefulness is triggered by the world outside. Consciousness can be defined as the observation of this inner mental space. We propose a new model, in which the state of the conscious observer is defined by the observer’s mental position and focus of attention. The mental position of the observer can either be within the mental self (intrapersonal space, in the mental outer world (extrapersonal space or in an empathic connection, i.e. within the intrapersonal space of another person (perspective taking. The focus of attention can be directed towards the self or towards the outside world. This mental space model can help us to understand the patterns of relationships and interactions with other persons as they occur in social life.To investigate the neurophysiological correlates and discriminability of the different mental states, we conducted an EEG experiment measuring the brain activity of 16 subjects via 64 electrodes while they engaged in different mental positions (intrapersonal, extrapersonal, perspective taking with different attentional foci (self, object. Compared to external mental locations, internal ones showed significantly increased alpha2 power, especially when the observer was focusing on an object. Alpha2 and beta2 were increased in the empathic condition compared to the extrapersonal perspective. Delta power was significantly higher when the attentional focus was directed towards an object in comparison to the participant’s own self. This exploratory study demonstrates highly significant differences between various mental locations and foci, suggesting that the proposed categories of mental location and intra- and interpersonal attentional foci are not only helpful theoretical concepts but are also physiologically relevant and therefore may relate to basic brain processing

  2. [Mental health care for immigrants in Germany]. (United States)

    Schouler-Ocak, M


    Immigrants represent a very heterogeneous population, with various stress factors for mental disorders. These individuals are confronted with numerous access barriers within the health care system, which are reflected in limited utilization of the mental health system and psychotherapy services. A particularly large gap in health service provision exists among refugees and asylum-seekers. There is an urgent need for action in terms of opening up of the mental health system, improving and simplifying routes of access, and facilitating treatment options.

  3. Our Sedation Experience on Mentally Retarded Patients


    Metin Alkan


    Aim: The majority of dental treatments can be performed under local anesthesia. However, sedation or general anesthesia are often required for mentally retarded patients presenting a lack of cooperation. The aim of this study was to retrospectively evaluate the outcomes of mentally retarded patients treated under sedation. Material and Method: The records of the 214 mentally retarded patients that were treated under sedation between 2010-2012 were retrospectively evaluated. The retrospective ...

  4. Salud mental en desastres naturales


    Bambarén Alatrista, Celso Bambarén; Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia. Lima,


    Los desastres se pueden considerar como un problema de salud pública que pueden afectar el comportamiento psicosocial de la población, especialmente de los grupos más vulnerables, como son los niños, adolescentes, mujeres, ancianos y personas con enfermedades físicas y mentales. Las personas desarrollan diferentes tipos de respuestas psicológicas al desastre según su capacidad de superación de la crisis inicial. El personal de salud tiene que identificar y cuidar a las personas que presenten ...

  5. Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders

    DEFF Research Database (Denmark)

    Wahlbeck, Kristian; Westman, Jeanette; Nordentoft, Merete;


    People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social policy and health service provision....

  6. New mental health indicators provide a snapshot on performance of the mental health system in Canada. (United States)

    Sandoval, Carolyn; Couris, Chantal; Leeb, Kira


    Although the general hospital remains an important place for stabilizing crises, most services for mental illnesses are provided in outpatient/community settings. In the absence of comprehensive data at the community level, data that are routinely collected from general hospitals can provide insights on the performance of mental health services for people living with mental illness or poor mental health. This article describes three new indicators that provide a snapshot on the performance of the mental health system in Canada: self-injury hospitalization rate, 30-day readmission rate for mental illness and percentage of patients with repeat hospitalizations for mental illness. Findings suggest a need for the early detection and treatment of mental illnesses and for optimal transitions between general hospitals and community services.

  7. Issues in consumer mental health information. (United States)

    Angier, J J


    Consumer health information as applied to mental health includes areas such as the diagnosis, management, and treatment of mental illness, as well as self-help, emotional wellness, and the relationship between life events, stress, and disease. This paper presents issues specific to the provision of mental health information to the layperson, e.g., confidentiality, literacy, competence, the social stigma of mental illness, the state of the art in psychiatry, popular psychology, and treatment fads. The development of a community education pamphlet illustrates how one organization addressed these issues.

  8. Orthopaedic Problems of the Mentally Retarded (United States)

    McSweeney, Anthony


    Problems encountered by orthopedic surgeons treating the mentally retarded are identified, and cooperation among pediatricians, psychiatrists, psychologists, social workers, physiotherapists, occupational therapists, and orthopedic surgeons is recommended. (GW)

  9. [Ergonomy and mental health at work.]. (United States)

    Dion-Hubert, C


    In the last ten years the concepts of health and mental health have been considerably modified and mental health at work is becoming an important interest of the in this field. However, it is difficult to establish with certainty the cause and effect between work and mental health problems since many other factors could possibly be responsible for the onset of those problems. Since work constitutes the principal activity of the human being it is reasonable that it could affect its mental equilibrium. Ergonomy deals with the person at work with the aim of better adapting the work to his needs, capacities and aspirations.

  10. Impact of organisational change on mental health

    DEFF Research Database (Denmark)

    Bamberger, Simon Grandjean; Vinding, Anker Lund; Larsen, Anelia


    Although limited evidence is available, organisational change is often cited as the cause of mental health problems. This paper provides an overview of the current literature regarding the impact of organisational change on mental health. A systematic search in PUBMED, PsychInfo and Web of Knowle......Although limited evidence is available, organisational change is often cited as the cause of mental health problems. This paper provides an overview of the current literature regarding the impact of organisational change on mental health. A systematic search in PUBMED, PsychInfo and Web...

  11. Childhood and adolescence: challenges in mental health. (United States)

    Shrivastava, Saurabh Rambiharilal; Shrivastava, Prateek Saurabh; Ramasamy, Jegadeesh


    Mental health is an integral and essential component of health. The World Health Organization (WHO) constitution states: "Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." More than 450 million people suffer from mental disorders worldwide. In India, mental health services, especially for children and adolescents, are limited both in terms of number of facilities as well as trained professionals. The majority of mental health services are restricted to urban areas, that is, medical colleges or regional mental health institutes. Mere presence of a treatment facility does not guarantee that all children/adolescents suffering from mental illness will utilize such services. In fact, most of the time there is a significant delay from the patient side in accessing mental health services either because of lack of awareness or associated stigma. It is high time to promote positive mental health in children, adolescents and their parents through health education. Parental counseling is of utmost importance in order to avoid the delay in treatment seeking.

  12. Older immigrants: language competencies and mental health. (United States)

    Taylor, Laura E; Taylor-Henley, Sharon; Doan, Lan


    Later-life immigration and a lack of dominant language competency present many challenges to mental health for older adults. English as a Second Language (ESL) classes for seniors, often regarded as the sole domain of ESL teachers, offer mental health professionals opportunities for mental health promotion and education. This paper examines some of the mental health issues that emerged from stories written by older adults in an ESL for Seniors program. The program is presented as an example of best practices in an ESL for Seniors program because of its specific development to meet the needs of ESL older persons.

  13. Mental health promotion in comprehensive schools. (United States)

    Onnela, A M; Vuokila-Oikkonen, P; Hurtig, T; Ebeling, H


    The purpose of this paper is to describe a participatory action research process on the development of a professional practice model of mental health nurses in mental health promotion in a comprehensive school environment in the city of Oulu, Finland. The developed model is a new method of mental health promotion for mental health nurses working in comprehensive schools. The professional practice model has been developed in workshops together with school staff, interest groups, parents and students. Information gathered from the workshops was analysed using action research methods. Mental health promotion interventions are delivered at three levels: universal, which is an intervention that affects the whole school or community; selective, which is an intervention focusing on a certain group of students; and indicated, which is an individually focused intervention. All interventions are delivered within the school setting, which is a universal setting for all school-aged children. The interventions share the goal of promoting mental health. The purposes of the interventions are enhancing protective factors, reducing risk factors relating to mental health problems and early identification of mental health problems as well as rapid delivery of support or referral to specialized services. The common effect of the interventions on all levels is the increase in the experience of positive mental health.

  14. What characterizes persons with poor mental health?

    DEFF Research Database (Denmark)

    Christensen, Anne Illemann; Davidsen, Michael; Kjøller, Mette;


    Background: The aim of the study was to identify and characterize groups with poor mental health defined by the SF-12 Mental Component Summary (MCS-12) scale. Methods: The study is based on the Danish Health and Morbidity Survey 2005 and includes 10,082 participants (16 years or older). Data were...... health were further characterized by being a heavy smoker, and having a BMI below 25. Women with poor mental health were further characterized by being 16-44 years old and sedentary in leisure time. CONCLUSIONS THE PREVALENCE OF POOR MENTAL HEALTH IS HIGHER AMONG WOMEN THAN MEN, AND DIFFERENT FACTORS...

  15. Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders

    DEFF Research Database (Denmark)

    Wahlbeck, Kristian; Westman, Jeanette; Nordentoft, Merete;


    People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social policy and health service provision.......People with mental disorders evince excess mortality due to natural and unnatural deaths. The relative life expectancy of people with mental disorders is a proxy measure of effectiveness of social policy and health service provision....

  16. International Observatory on Mental Health Systems: a mental health research and development network


    Minas Harry


    Abstract Background While the mental health situation for most people in low and middle-income countries is unsatisfactory, there is a renewed commitment to focus attention on the mental health of populations and on the scaling up of mental health services that have the capacity to respond to mental health service needs. There is general agreement that scaling up activities must be evidence-based and that the effectiveness of such activities must be evaluated. If these requirements are to be ...

  17. Diagnosis and treatment of mental illness in mentally retarded children: a developmental model. (United States)

    Dosen, A


    Attempts have been made in recent years to discover the roots of psychiatric disorders in mentally retarded children by employing a developmental approach in which the child, not the handicap, is brought more clearly into focus. This paper provides a brief overview of the developmental model that has proven useful for the author in the psychiatric diagnosis of mentally retarded children. Application of this model to the treatment of mentally ill-mentally retarded children is also addressed.

  18. Mental Health Mobile Apps: From Infusion to Diffusion in the Mental Health Social System. (United States)

    East, Marlene Lynette; Havard, Byron C


    The roles of mental health educators and professionals in the diffusion of mental health mobile apps are addressed in this viewpoint article. Mental health mobile apps are emerging technologies that fit under the broad heading of mobile health (mHealth). mHealth, encompassed within electronic health (eHealth), reflects the use of mobile devices for the practice of public health. Well-designed mental health mobile apps that present content in interactive, engaging, and stimulating ways can promote cognitive learning, personal growth, and mental health enhancement. As key influencers in the mental health social system, counselor educators and professional associations may either help or hinder diffusion of beneficial mHealth technologies. As mental health mobile apps move towards ubiquity, research will continue to be conducted. The studies published thus far, combined with the potential of mental health mobile apps for learning and personal growth, offer enough evidence to compel mental health professionals to infuse these technologies into education and practice. Counselor educators and professional associations must use their influential leadership roles to train students and practitioners in how to research, evaluate, and integrate mental health mobile apps into practice. The objectives of this article are to (1) increase awareness of mHealth and mental health mobile apps, (2) demonstrate the potential for continued growth in mental health mobile apps based on technology use and acceptance theory, mHealth organizational initiatives, and evidence about how humans learn, (3) discuss evidence-based benefits of mental health mobile apps, (4) examine the current state of mHealth diffusion in the mental health profession, and (5) offer solutions for impelling innovation diffusion by infusing mental health mobile apps into education, training, and clinical settings. This discussion has implications for counselor educators, mental health practitioners, associations

  19. Transitions: A Mental Health Literacy Program for Postsecondary Students (United States)

    Potvin-Boucher, Jacqueline; Szumilas, Magdalena; Sheikh, Tabinda; Kutcher, Stan


    Enhancement of mental health literacy is a mental health promotion strategy that may be effective at destigmatizing mental illness and increasing self-seeking behavior. Transitions is a mental health literacy program intended to heighten students' awareness and discussion of mental health problems and promote help-seeking behaviors. Transitions…

  20. The global burden of mental disorders : An update from the WHO World Mental Health (WMH) Surveys

    NARCIS (Netherlands)

    Kessler, Ronald C.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Chatterji, Somnath; Lee, Sing; Ormel, Johan; Uestuen, T. Bedirhan; Wang, Philip S.


    Aims - The paper reviews recent findings from the WHO World Mental Health (WMH) surveys oil the global burden of mental disorders. Methods - The WMH surveys are representative community surveys in 28 countries throughout the world aimed at providing information to mental health policy makers about t

  1. Deinstitutionalization: Its Impact on Community Mental Health Centers and the Seriously Mentally Ill (United States)

    Kliewer, Stephen P.; McNally Melissa; Trippany, Robyn L.


    Deinstitutionalization has had a significant impact on the mental health system, including the client, the agency, and the counselor. For clients with serious mental illness, learning to live in a community setting poses challenges that are often difficult to overcome. Community mental health agencies must respond to these specific needs, thus…

  2. Racial Disparities in Mental Health Outcomes after Psychiatric Hospital Discharge among Individuals with Severe Mental Illness (United States)

    Eack, Shaun M.; Newhill, Christina E.


    Racial disparities in mental health outcomes have been widely documented in noninstitutionalized community psychiatric samples, but few studies have specifically examined the effects of race among individuals with the most severe mental illnesses. A sample of 925 individuals hospitalized for severe mental illness was followed for a year after…

  3. Mental Illness and Mental Health: The Two Continua Model Across the Lifespan

    NARCIS (Netherlands)

    Westerhof, Gerben J.; Keyes, Cory L.M.


    Mental health has long been defined as the absence of psychopathologies, such as depression and anxiety. The absence of mental illness, however, is a minimal outcome from a psychological perspective on lifespan development. This article therefore focuses on mental illness as well as on three core co

  4. The global burden of mental disorders: An update from the WHO World Mental Health (WMH) Surveys

    NARCIS (Netherlands)

    Kessler, R.C.; Aguilar-Gaxiola, S.; Alonso, J.; Chatterji, S.; Lee, S.; Ormel, J.; Ustun, T.B.; Wang, P.S.


    Aims - The paper reviews recent findings from the WHO World Mental Health (WMH) surveys oil the global burden of mental disorders. Methods - The WMH surveys are representative community surveys in 28 countries throughout the world aimed at providing information to mental health policy makers about t

  5. Consultations for mental problems in general practices with and without mental health nurses.

    NARCIS (Netherlands)

    Magnée, T.; Beurs, D. de; Verhaak, P.


    Background & Aim: It seems cost-effective to provide mental health care to patient with mild mental problems in general practices instead of in specialized care, but general practitioners (GPs) often lack time or expertise. Since 2008, Dutch GPs have been collaborating with nurses with mental health

  6. Factors Promoting Mental Health of Adolescents Who Have a Parent with Mental Illness: A Longitudinal Study (United States)

    Van Loon, L. M. A.; Van De Ven, M. O. M.; Van Doesum, K. T. M.; Hosman, C. M. H.; Witteman, C. L. M.


    Background: Children of parents with mental illness have an elevated risk of developing a range of mental health and psychosocial problems. Yet many of these children remain mentally healthy. Objective: The present study aimed to get insight into factors that protect these children from developing internalizing and externalizing problems. Methods:…

  7. Factors promoting mental health of adolescents who have a parent with mental illness: A longitudinal study

    NARCIS (Netherlands)

    Loon, L.M.A. van; Ven, M.O.M. van de; Doesum, K.T.M. van; Hosman, C.M.H.; Witteman, C.L.M.


    Children of parents with mental illness have an elevated risk of developing a range of mental health and psychosocial problems. Yet many of these children remain mentally healthy. The present study aimed to get insight into factors that protect these children from developing internalizing and extern

  8. Memory updating and mental arithmetic

    Directory of Open Access Journals (Sweden)

    Cheng-Ching eHan


    Full Text Available Is domain-general memory updating ability predictive of calculation skills or are such skills better predicted by the capacity for updating specifically numerical information? Here, we used multidigit mental multiplication (MMM as a measure for calculating skill as this operation requires the accurate maintenance and updating of information in addition to skills needed for arithmetic more generally. In Experiment 1, we found that only individual differences with regard to a task updating numerical information following addition (MUcalc could predict the performance of MMM, perhaps owing to common elements between the task and MMM. In Experiment 2, new updating tasks were designed to clarify this: a spatial updating task with no numbers, a numerical task with no calculation, and a word task. The results showed that both MUcalc and the spatial task were able to predict the performance of MMM but only with the more difficult problems, while other updating tasks did not predict performance. It is concluded that relevant processes involved in updating the contents of working memory support mental arithmetic in adults.

  9. Mental Representations in Art Discourse

    Directory of Open Access Journals (Sweden)

    Katja Sudec


    Full Text Available The paper starts by examining the content included in the museum environment, where I write about the type of relations that emerge in a museum or artistic setting. This is followed by an observation of a social act (socialising and a chapter on the use of food in an artistic venue. At the end, I address art education via the format that I developed at the 6th Berlin Biennale. This is followed by an overview of the cognitive model of the fort-da game based on Freud’s theory via two discourse models. Here, I address discourse on art works in the form of a lecture or reading, where the art space is fictitiously present, and then move on to discuss discourse on art works in real, “present” art space. This is followed by a section on actions (Handlungen in German and methods supporting the fort-da model. The last part of the article examines the issue of “mental representations”, defining and explaining the function of mental representations with regard to the target audience of the blind and visually impaired.

  10. Mental Mechanisms for Topics Identification

    Directory of Open Access Journals (Sweden)

    Louis Massey


    Full Text Available Topics identification (TI is the process that consists in determining the main themes present in natural language documents. The current TI modeling paradigm aims at acquiring semantic information from statistic properties of large text datasets. We investigate the mental mechanisms responsible for the identification of topics in a single document given existing knowledge. Our main hypothesis is that topics are the result of accumulated neural activation of loosely organized information stored in long-term memory (LTM. We experimentally tested our hypothesis with a computational model that simulates LTM activation. The model assumes activation decay as an unavoidable phenomenon originating from the bioelectric nature of neural systems. Since decay should negatively affect the quality of topics, the model predicts the presence of short-term memory (STM to keep the focus of attention on a few words, with the expected outcome of restoring quality to a baseline level. Our experiments measured topics quality of over 300 documents with various decay rates and STM capacity. Our results showed that accumulated activation of loosely organized information was an effective mental computational commodity to identify topics. It was furthermore confirmed that rapid decay is detrimental to topics quality but that limited capacity STM restores quality to a baseline level, even exceeding it slightly.

  11. [Empathy in severe mental disorders]. (United States)

    Martin-Contero, M C; Secades-Villa, R; Aparicio-Migueza, A; Tirapu-Ustarroz, J


    Introduccion. La empatia es un subproceso de la cognicion social que se define como la capacidad de comprender y compartir los pensamientos, deseos y sentimientos de otra persona, y es crucial en muchas formas de interaccion social adaptativa. Es un fenomeno contextual, flexible y multidimensional que se relaciona con diferentes procesos y redes neuronales. Objetivo. Evaluar la empatia en una muestra de sujetos con diagnosticos que se engloban dentro de la categoria de trastorno mental grave en tratamiento en un programa de rehabilitacion psicosocial. Sujetos y metodos. Participaron 22 personas con trastorno mental grave en tratamiento en programas de rehabilitacion psicosocial y 22 controles sanos. Se aplico a cada sujeto una bateria de pruebas: cociente de empatia, Reading the Mind in the Eyes Test (test de la mirada) e indice de reactividad interpersonal. Resultados. En el test de la mirada, el grupo experimental puntuo significativamente menos que el grupo control (t = 2,8; p empatia; sin embargo, muestran dificultades a la hora de reconocer estados emocionales mediante la mirada, lo que indica un procesamiento de la informacion para las caras diferente a los sujetos de la poblacion normal.

  12. Debt trajectories and mental health. (United States)

    Hojman, Daniel A; Miranda, Álvaro; Ruiz-Tagle, Jaime


    In the last few decades, there was a marked increase in consumer debt in the United States, Latin America and other emerging countries, spurring a debate about the real costs and benefits of household credit. Using a unique longitudinal dataset with detailed health and balance sheet information from a large sample of 10,900 Chilean households we study the relationship between debt trajectories in a three-year time window and mental health. We find that depressive symptoms are higher for those who have been persistently over-indebted, followed by those who transit from moderate to high debt levels. We also find that those who transition from over-indebtedness to moderate debt levels have no additional depressive symptoms compared to those with trajectories of moderate debt throughout (never over-indebted). This suggests that the debt-related contribution to depressive symptoms vanishes as debt levels fall. The association between debt and depressive symptoms seems to be driven by non-mortgage debt -primarily consumer credit- or late mortgage payments; secured debt (secured by collateral) per se is not associated with depressive symptoms. Policy interventions to reduce the negative association of over-indebtedness on mental health are discussed.

  13. Mental preparation for hockey players : study on self-talk and mental imagary


    Allenius, Jani; Lehtonen, Matias


    This bachelor thesis is a study of mental preparation, and how to go it through with players. Objective is to find easy way to start teaching mental preparation for players and two main themes were mental imagery and self-talk. This report includes theory part of different consepts of mental preparation and extensive theory parts of mental imagery and self-talk. The practical section is made of the lessons that players were taught during the season and assignment that they were given. The ...

  14. [The sainsbury centre for mental health: forensic mental health services in England and wales]. (United States)

    Rutherford, M; Duggan, S


    The Sainsbury Centre for Mental Health (SCMH) is a charity founded in 1985 by Gatsby Charitable Foundation. The SCMH works to improve the quality of life for people with mental health problems by influencing policy and practice in mental health and related services. Working to improve the quality of mental health care for people in prison is one of SCMH main work theme. This paper describes some epidemiological aspects of mental health situation of prisoners in England and Wales and the available forensic facilities to manage this kind of patients in prison.

  15. Resisting the Stigma of Mental Illness (United States)

    Thoits, Peggy A.


    The relationship between stigmatization and the self-regard of patients/consumers with mental disorder is negative but only moderate in strength, probably because a subset of persons with mental illness resists devaluation and discrimination by others. Resistance has seldom been discussed in the stigma and labeling literatures, and thus conditions…

  16. Students' Mental Models of Atomic Spectra (United States)

    Körhasan, Nilüfer Didis; Wang, Lu


    Mental modeling, which is a theory about knowledge organization, has been recently studied by science educators to examine students' understanding of scientific concepts. This qualitative study investigates undergraduate students' mental models of atomic spectra. Nine second-year physics students, who have already taken the basic chemistry and…

  17. Externalising Students' Mental Models through Concept Maps (United States)

    Chang, Shu-Nu


    The purpose of this study is to use concept maps as an "expressed model" to investigate students' mental models regarding the homeostasis of blood sugar. The difficulties in learning the concept of homeostasis and in probing mental models have been revealed in many studies. Homeostasis of blood sugar is one of the themes in junior high school…

  18. Mental Health Concerns: Veterans & Active Duty (United States)

    ... crisis—particularly if it’s a life-threatening mental health crisis—you should proceed immediately to a military or civilian emergency room for acute care or call 911. How Will Asking for Mental Health Treatment Affect My Career? Military personnel have always ...

  19. Needs of people with severe mental illness

    NARCIS (Netherlands)

    Wiersma, D


    Objective: This study reviews conceptual and methodological issues of needs for care among people with severe mental illness (SMI) and presents data on their prevalence, correlates and consequences for mental health care. Method: Focus is on the definition of the concept of need as what people can b

  20. Supplemental Security Income Benefits for Mental Disorders. (United States)

    Perrin, James M; Houtrow, Amy; Kelleher, Kelly; Hoagwood, Kimberly; Stein, Ruth E K; Zima, Bonnie


    The Supplemental Security Income Program (SSI) provides financial support to low-income households with children and youth with severe disabilities. The program included children when it began in the early 1970s. The numbers of children receiving SSI benefits increased substantially in the early 1990s, in part through an expansion of the listings of mental health conditions with which children could become eligible. Over the past 20 years, larger numbers of children have received SSI benefits for mental disorders, and these increases have led to questions from the press and Congress regarding these numbers. Do they indicate more of an increase in mental disorders among SSI children than in the general population? The National Academy of Medicine (NAM; formerly the Institute of Medicine) convened a study panel to examine what is known about mental disorders among the child SSI population and how that compares with evidence about mental disorders in children in general. The NAM report provides detailed information about how SSI works, about the changing numbers of children receiving SSI for mental disorders, and some comparisons with other evidence about rising rates of mental disorders in the general population and especially among children living in poverty. The report indicates that increasing numbers of children with mental disorders in SSI mirror similar increases in the population in general. This article summarizes key evidence from the NAM report and suggests the implications for pediatricians.

  1. Measuring Mental Imagery with Visual Analogue Scales. (United States)

    Quilter, Shawn M.; Band, Jennie P.; Miller, Gary M.


    Investigates some of the psychometric characteristics of the results from visual-analogue scales used to measure mental imagery. Reports that the scores from visual-analogue scales are positively related to scores from longer pencil-and-paper measures of mental imagery. Implications and limitations for the use of visual-analogue scales to measure…

  2. Promoting School-Wide Mental Health (United States)

    Trussell, Robert P.


    Although schools are not traditionally designed to provide intensive mental health services to children, they are in a position to create systems that foster mental health. By creating school-wide systems in which students are academically, behaviorally and socially successful, schools can integrate those essential protective factors shown to…

  3. Determining mental load through measuring brain signals

    NARCIS (Netherlands)

    Brouwer, A.M.; Erp, J.B.F. van


    How can you tell whether someone working or gaming is mentally taxed too high or too low? In collaboration with Noldus IT (Wageningen) and the FC Donders Institute (Nijmegen), TNO designed and conducted an experiment to measure mental load through brain signals. 35 participants performed a computer

  4. Migrant Farmworker Stress: Mental Health Implications (United States)

    Hiott, Ann E.; Grzywacz, Joseph G.; Davis, Stephen W.; Quandt, Sara A.; Arcury, Thomas A.


    Context: The number of Latinos in rural regions of the United States is increasing. Little is known about factors that undermine the mental health of this segment of the rural population. Purpose: The goal of this study is to determine which stressors inherent in farmwork and the farmworker lifestyle contribute to poor mental health. Methods: An…

  5. Mental health of Turkish women in Germany

    DEFF Research Database (Denmark)

    Bromand, Z; Temur-Erman, S; Yesil, R;


    The purpose of the present study was to examine the protective and risk factors of mental distress among Turkish women living in Germany.......The purpose of the present study was to examine the protective and risk factors of mental distress among Turkish women living in Germany....

  6. Mental and physical effort affect vigilance differently

    NARCIS (Netherlands)

    Smit, A.S.; Eling, P.A.T.M.; Hopman, M.T.E.; Coenen, A.M.L.


    Both physical and mental effort are thought to affect vigilance. Mental effort is known for its vigilance declining effects, but the effects of physical effort are less clear. This study investigated whether these two forms of effort affect the EEG and subjective alertness differently. Participants

  7. Mental and physical effort affect vigilance differently.

    NARCIS (Netherlands)

    Smit, A.S.; Eling, P.A.T.M.; Hopman, M.T.E.; Coenen, A.M.L.


    Both physical and mental effort are thought to affect vigilance. Mental effort is known for its vigilance declining effects, but the effects of physical effort are less clear. This study investigated whether these two forms of effort affect the EEG and subjective alertness differently. Participants

  8. Human Sexuality for the Mentally Retarded. (United States)

    Zitzow, Darryl; And Others

    The Human Sexuality for the Mentally Retarded program sought to provide cognitive awareness of human sexuality for mentally retarded trainable residents (5 to 21 years old) as well as inservice staff training regarding attitudes and cognitive awareness changes. Cognitive awareness training focused on body parts, discrimination of the sexes,…

  9. Millennial Students' Mental Models of Information Retrieval (United States)

    Holman, Lucy


    This qualitative study examines first-year college students' online search habits in order to identify patterns in millennials' mental models of information retrieval. The study employed a combination of modified contextual inquiry and concept mapping methodologies to elicit students' mental models. The researcher confirmed previously observed…

  10. Manual Training of Mental Rotation in Children (United States)

    Wiedenbauer, Gunnar; Jansen-Osmann, Petra


    When deciding whether two stimuli rotated in space are identical or mirror reversed, subjects employ mental rotation to solve the task. In children mental rotation can be trained by extensive repetition of the task, but the improvement seems to rely on the retrieval of previously learned stimuli. We assumed that due to the close relation between…

  11. Motor Processes in Children's Mental Rotation (United States)

    Frick, Andrea; Daum, Moritz M.; Walser, Simone; Mast, Fred W.


    Previous studies with adult human participants revealed that motor activities can influence mental rotation of body parts and abstract shapes. In this study, we investigated the influence of a rotational hand movement on mental rotation performance from a developmental perspective. Children at the age of 5, 8, and 11 years and adults performed a…

  12. Positive Mental Health; measurement, relevance and implications

    NARCIS (Netherlands)

    Lamers, Sanne


    The professionalization of psychology yielded many advantages, but also led to a main focus on psychopathology in mental health care. This thesis investigated an additional positive approach to mental health, focusing on positive feelings and life satisfaction (emotional well-being) and optimal func

  13. Segmenting the mental health care market. (United States)

    Stone, T R; Warren, W E; Stevens, R E


    The authors report the results of a segmentation study of the mental health care market. A random sample of 387 residents of a western city were interviewed by telephone. Cluster analysis of the data identified six market segments. Each is described according to the mental health care services to which it is most sensitive. Implications for targeting the segments are discussed.

  14. Five Keys for Teaching Mental Math (United States)

    Olsen, James R.


    After studying the Common Core State Standards for Mathematics (CCSSM) and brain-based learning research, James Olsen believes mental math instruction in secondary school mathematics (grades 7-12) and in teacher education programs needs increased attention. The purpose of this article is to share some keys for teaching mental math. Olsen also…

  15. Mental Imagery in Creative Problem Solving. (United States)

    Polland, Mark J.

    In order to investigate the relationship between mental imagery and creative problem solving, a study of 44 separate accounts reporting mental imagery experiences associated with creative discoveries were examined. The data included 29 different scientists, among them Albert Einstein and Stephen Hawking, and 9 artists, musicians, and writers,…

  16. Calcineurin activity in children with Mental handicap. (United States)

    Bindu, L Hema; Rani, P Usha; Reddy, P P


    Calcineurin, a Ca(2+)-Calmodulin dependent protein phosphatase, is important for Ca(2+) mediated signal transduction. The main objective of this study was to examine the potential role of calcineurin in idiopathic mental handicap. Calcineurin levels were estimated in 20 children in the age group of 5-16 years with idiopathic mental handicap attending the Special. Education Centre for the Mentally Handicapped in Hyderabad. The results of the present study showed decreased activity of serum calcineurin in children with idiopathic mental handicap compared to those of normal subjects in the same age group. The observations thus suggest impaired calcineurin activity in children with mental handicap. Calcineurin that is involved in biosynthesis and release of neurotransmitters at the synaptic terminal brain is affected thereby causing brain damage and leading to mental handicap. Impaired calcineurin activity was already indicated in many human diseases such as Down's syndrome, Alzheimers, Brain ischemia, cardiac hypertrophy etc. It is therefore necessary to check the calcineurin levels in children with mental handicap to understand the role of calcineurin in the causation of Mental handicap.

  17. Mental health expectancy--the European perspective

    DEFF Research Database (Denmark)

    Jagger, C; Ritchie, K; Brønnum-Hansen, Henrik


    The increase in life expectancy observed over the last decade has particular relevance for mental health conditions of old age, such as dementia. Although mental disorders have been estimated to be responsible for 60% of all disabilities, until recently population health indicators such as health...

  18. Team management in community mental health. (United States)

    McGuinness, M


    The community mental health team is now the established model for mental health service delivery in the community. Managing CMHTs requires a diverse range of managerial skills, role clarity and authority. More research needs to be undertaken on the role and effectiveness of the CMHT manager.

  19. Environmental Quality Index and Childhood Mental Health (United States)

    Childhood mental disorders affect between 13%-20% of children in the United States (US) annually and impact the child, family, and community. Literature suggests associations exist between environmental and children’s mental health such as air pollution with autism and ADHD...

  20. Mental Health of Students. Position Statement. Revised (United States)

    National Association of School Nurses (NJ1), 2008


    It is the position of the National Association of School Nurses (NASN) that mental health is as critical to academic success as physical well-being. School nurses play a vital role in the school community by promoting positive mental health development in students through school/community-based programs and curricula. As members of…

  1. Team learning: building shared mental models

    NARCIS (Netherlands)

    Bossche, van den P.; Gijselaers, W.; Segers, M.; Woltjer, G.B.; Kirschner, P.


    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning

  2. Team Learning: Building Shared Mental Models (United States)

    Van den Bossche, Piet; Gijselaers, Wim; Segers, Mien; Woltjer, Geert; Kirschner, Paul


    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning behaviors and team effectiveness. Analyses were…

  3. Theories of Dual Diagnosis in Mental Retardation. (United States)

    Matson, Johnny L.; Sevin, Jay A.


    Provides historical review of theory development in the field of dual diagnosis, defined as co-occurrence of mental health disorders with mental retardation. Noting that current etiological theories have practical implications for treatment and prevention of dual diagnosis, discusses current status of etiological theories and future directions for…

  4. Spirituality and Mental Health among Homeless Mothers (United States)

    Hodge, David R.; Moser, Stephanie E.; Shafer, Michael S.


    Mothers are one of the fastest growing segments of the homeless population in the United States. Although mental health problems often contribute to homelessness, little is known about the factors that affect mothers' mental health. To help identify protective factors, this longitudinal study examined the relationship between spirituality and…

  5. Ethics and mental illness research. (United States)

    Roberts, Laura Weiss


    There are many tasks ahead in the area of ethics and mental illness research. We face unknown challenges in psychiatric genetics projects, studies of psychopharmacological interventions in children, controversial scientific designs (e.g., symptom challenge, medication-free interval), and cross-disciplinary research incorporating goals and methods of health services, epidemiology, and social and behavioral science endeavors. Boundaries between innovative clinical practices and research-related experimentation will become increasingly difficult to distinguish, as will the roles between clinicians, clinical researchers, and basic scientists. Moreover, the institutions and systems in which research occurs are being rapidly and radically revised, raising new questions about oversight responsibilities and standards. Our ability to identify and respond to the ethical questions arising in this uncharted territory will depend on our willingness to self-reflect, to integrate the observations and insights of the past century, to think with great clarity, and to anticipate novel ethical problems that keep company with scientific advancements. It will also depend on data. Empirical study of ethical dimensions of human research is essential to anchor and attune the intuitions and theoretical constructs that we develop. Science and ethics have changed over the past 100 years, as they will over the next century. It is ironic that the ethical acceptability of psychiatric research is so much in question at this time, when it holds so much promise for advancing our understanding of mental illness and its treatment. The tension between the duty to protect vulnerable individuals and the duty to perform human science will continue to grow, as long as ethics and science are seen as separable, opposing forces with different aims championed by different heroes. The profession of psychiatry is poised to move toward a new, more coherent research ethics paradigm in which scientific and

  6. Psychometric properties of a Mental Health Team Development Audit Tool.

    LENUS (Irish Health Repository)

    Roncalli, Silvia


    To assist in improving team working in Community Mental Health Teams (CMHTs), the Mental Health Commission formulated a user-friendly but yet-to-be validated 25-item Mental Health Team Development Audit Tool (MHDAT).

  7. Mental health system historians: adults with schizophrenia describe changes in community mental health care over time. (United States)

    Stein, Catherine H; Leith, Jaclyn E; Osborn, Lawrence A; Greenberg, Sarah; Petrowski, Catherine E; Jesse, Samantha; Kraus, Shane W; May, Michael C


    This qualitative study examined changes in community mental health care as described by adults diagnosed with schizophrenia with long-term involvement in the mental health system to situate their experiences within the context of mental health reform movements in the United States. A sample of 14 adults with schizophrenia who had been consumers of mental health services from 12 to 40 years completed interviews about their hospital and outpatient experiences over time and factors that contributed most to their mental health. Overall, adults noted gradual changes in mental health care over time that included higher quality of care, more humane treatment, increased partnership with providers, shorter hospital stays, and better conditions in inpatient settings. Regardless of the mental health reform era in which they were hospitalized, participants described negative hospitalization experiences resulting in considerable personal distress, powerlessness, and trauma. Adults with less than 27 years involvement in the system reported relationships with friends and family as most important to their mental health, while adults with more than 27 years involvement reported mental health services and relationships with professionals as the most important factors in their mental health. The sample did not differ in self-reported use of services during their initial and most recent hospitalization experiences, but differences were found in participants' reported use of outpatient services over time. Findings underscore the importance of the lived experience of adults with schizophrenia in grounding current discourse on mental health care reform.

  8. Remote State Preparation of Mental Information

    CERN Document Server

    Tressoldi, Patrizio E


    The aim of this paper is to define in theoretical terms and summarise the available experimental evidence that physical and mental "objects", if considered "information units", may present similar classical and quantum models of communication beyond their specific characteristics. Starting with the Remote State Preparation protocol, a variant of the Teleportation protocol, for which formal models and experimental evidence are already available in quantum mechanics, we outline a formal model applied to mental information we defined Remote State Preparation of Mental Information (RSPMI), and we summarise the experimental evidence supporting the feasibility of a RSPMI protocol. The available experimental evidence offers strong support to the possibility of real communication at distance of mental information promoting the integration between disciplines that have as their object of knowledge different aspects of reality, both physical and the mental, leading to a significant paradigm shift in cognitive and infor...


    Directory of Open Access Journals (Sweden)

    Vasilka GALEVSKA


    Full Text Available Mental retardation is a complex individual and social problem. According to WHO, around 1-3 % of world population are mentally retarded people and the percentage between school children is around 2 %.The development of a mentally retarded child depends on factors related to the disability itself, all the limitations and characteristics which results from that. But, physical, psychical, educational and social development of a mentally retarded child, also, depend on other conditions, such as the family and the wider environment, their reactions, attitudes, awareness and sensitivity for special needs of the child, as well as their preparedness and possibilities to respond.At the same time, it is necessary that the mentally retarded child is detected and diagnosed in time, as well as the early start of an adequate treatment.

  10. Mental health surveillance and information systems. (United States)

    Gater, R; Chisholm, D; Dowrick, C


    Routine information systems for mental health in many Eastern Mediterranean Region countries are rudimentary or absent, making it difficult to understand the needs of local populations and to plan accordingly. Key components for mental health surveillance and information systems are: national commitment and leadership to ensure that relevant high quality information is collected and reported; a minimum data set of key mental health indicators; intersectoral collaboration with appropriate data sharing; routine data collection supplemented with periodic surveys; quality control and confidentiality; and technology and skills to support data collection, sharing and dissemination. Priority strategic interventions include: (1) periodically assessing and reporting the mental health resources and capacities available using standardized methodologies; (2) routine collection of information and reporting on service availability, coverage and continuity, for priority mental disorders disaggregated by age, sex and diagnosis; and (3) mandatory recording and reporting of suicides at the national level (using relevant ICD codes).

  11. Refugee children: mental health and effective interventions. (United States)

    Pacione, Laura; Measham, Toby; Rousseau, Cécile


    The mental health consequences of war and other forms of organized violence for children represent a serious global public health issue. Much of the research on the mental health of war-affected civilians has focused on refugees who have sought asylum in high-income countries and face the dual stress of a traumatic past and resettlement. This review will focus on the mental health of refugee children who have fled war as well as interventions to both prevent and treat adverse mental health outcomes. While war can have devastating mental health consequences, children raised in the midst of armed conflict also display resilience. Effective interventions for refugee children will be discussed both in terms of prevention and treatment of psychopathology, with a focus on recent developments in the field.

  12. [Stress, mental disorders and coronary heart disease]. (United States)

    Lederbogen, F; Ströhle, A


    There are numerous associations between stress, mental disorders and coronary heart disease (CHD). Exposure to an acute stressor leads to activation of the hypothalamus-pituitary-adrenal and sympathoadrenal systems and chronic stressors are associated with sustained functional changes of these systems. Experiencing acute and chronic stress is paralleled by an increased incidence of mental disorders with the most consistent evidence on the triggering of major depressive episodes. Various mental disorders, including depression, anxiety and schizophrenia, are associated with an increased risk of CHD. Furthermore, acute and chronic stressors have been identified as risk factors or triggers of acute coronary syndromes. Thus therapeutic strategies aim at reducing subjective stress experience, therapy of mental disorders and treatment of cardiac risk factors known to be more prevalent in increased stress states and mental disorders.


    Directory of Open Access Journals (Sweden)

    Gleide Santos de Araújo


    Full Text Available Despite having vaccine and treatment , TB remains a public health problem . Publications have described high proportion of TB among people with anxiety , depression and mental disorders . This study aimed to identify publications on the association between common mental disorders and tuberculosis and describe the state of the art . This is a literature review with keywords tuberculosis,common mental disorders , anxiety and depression , we excluded studies of extra- pulmonary tuberculosis and animals. 09 articles, only on a specific common mental disorders , comparing the proportion of these in tuberculosis cases ( 46.7 % and tuberculosis infected by the human immunodeficiency virus ( 63.7 % , there are few studies concerning the topic were elected , the most specific problems of anxiety and depression , are from countries where the incidence of tuberculosis is high, ethodological strategies have low analytical power and do not investigate the causal mechanisms underlying the relationship between mental health and tuberculosis.

  14. Insomnia and mental health in college students. (United States)

    Taylor, Daniel J; Gardner, Christie E; Bramoweth, Adam D; Williams, Jacob M; Roane, Brandy M; Grieser, Emily A; Tatum, Jolyn I


    Insomnia is strongly associated with certain mental health problems in the general population. However, there is little research examining this relation in young adults-an age group where many mental health problems first present. This study examined relations between insomnia and mental health symptoms in a college population (N = 373; 60.9% women; mean age of 21 years). Insomnia was assessed via self-report and sleep diaries, and mental health was assessed via the Symptom Check List-90. Analyses revealed insomnia was prevalent (9.4%), and these young adults had significantly more mental health problems than those without insomnia, although some significant results were lost after controlling for comorbid health problems.

  15. Involuntary detention and treatment of the mentally ill: China's 2012 Mental Health Law. (United States)

    Ding, Chunyan


    The long-awaited Mental Health Law of China was passed on 26 October 2012 and took effect on 1 May 2013. Being the first national legislation on mental health, it establishes a basic legal framework to regulate mental health practice and recognizes the fundamental rights of persons with mental disorders. This article focuses on the system of involuntary detention and treatment of the mentally ill under the new law, which is expected to prevent the so-called "Being misidentified as mentally disordered" cases in China. A systematic examination of the new system demonstrates that the Mental Health Law of China implicitly holds two problematic assumptions and does not provide adequate protection of the fundamental rights of the involuntary patients. Administrative enactments and further national legislative efforts are needed to remedy these flaws in the new law.

  16. Disease: H00269 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00269 Primary microcephaly (MCPH) Autosomal recessive primary microcephaly (MCPH) ...t brain growth. Trends Mol Med 12:358-66 (2006) PMID:15806441 Woods CG, Bond J, Enard W Autosomal recessive

  17. EST Table: BY921544 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 ovS0 ...

  18. EST Table: DC540266 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 dpe- ...

  19. EST Table: FS929848 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available DICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterole...1| PREDICTED: similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

  20. EST Table: FS936166 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available ar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) ... similar to Low density lipoprotein receptor adapter protein 1 (Autosomal recessive hypercholesterolemia protein) isoform 1 [Tribolium castaneum] FS929848 fwgP ...

  1. [Mental disorders and diabetes mellitus]. (United States)

    Abrahamian, Heidemarie; Kautzky-Willer, Alexandra; Rießland-Seifert, Angelika; Fasching, Peter; Ebenbichler, Christoph; Hofmann, Peter; Toplak, Hermann


    Psychiatric disorders and psychological problems are common in patients with diabetes mellitus. There is a twofold increase in depression which is associated with suboptimal glycemic control and increased morbidity and mortality. Other psychiatric disorders with a higher incidence of diabetes mellitus are cognitive impairment, dementia, disturbed eating behaviour, anxiety disorders, schizophrenia, bipolar disorders and borderline personality disorder. The coincidence of mental disorders and diabetes mellitus has unfavourable influences on metabolic control and micro- and macroangiopathic late complications. Improvement of therapeutic outcome is a challenge in the modern health care system. The intentions behind this position paper are to rise awareness of this special set of problems, to intensify cooperation between involved health care providers and to reduce incidence of diabetes mellitus as well as morbidity and mortality from diabetes in this patient group.

  2. Mental vulnerability as a risk factor for depression

    DEFF Research Database (Denmark)

    Østergaard, Ditte; Dalton, Susanne Oksbjerg; Bidstrup, Pernille Envold;


    Mental vulnerability (i.e. a tendency to experience psychosomatic symptoms, mental symptoms or interpersonal problems) is associated with various diseases. This study investigated whether mental vulnerability is associated with hospitalization for depression.......Mental vulnerability (i.e. a tendency to experience psychosomatic symptoms, mental symptoms or interpersonal problems) is associated with various diseases. This study investigated whether mental vulnerability is associated with hospitalization for depression....

  3. Relationship between mental health and marital satisfaction

    Directory of Open Access Journals (Sweden)

    Abdolsattar Shahi


    Full Text Available Background: Marital satisfaction is an important component of the marriage. Mental health as a component of the personal characteristic also related with marital satisfaction. The aim of this study was to investigate the association between mental health and marital satisfaction of couples.Methods: Three hundred couples from high-risk area of Gorgan – North of Iran were selected. Association between men's and women’s mental health level was measured using General Health Questionnaire-28 (GHQ-28. Marital satisfaction measured by Enrich Marital Satisfaction Questionnaire among married couples. Data was analyzed using multiple regression and analysis of variance modelling.Results: Results indicated that marital satisfaction was predicted by the person’s mental health level. Findings also showed that depression and anxiety were significantly associated with marital satisfaction. 52.5% of studied individuals had mental disorders at the clinical level (p≤0/05. Marital satisfaction in this population was 51.7%. Conclusions: The study confirmed that mental health is an important predictor of marital satisfaction. Improving mental health may lead to improve marital satisfaction.

  4. [Family, Through Mental Health and Sickness]. (United States)

    Solano Murcia, Martha Inés; Vasquez Cardozo, Socorro


    The following article arises from the study "Representaciones sociales en el campo de la salud mental" (Social Representations in the Mental Health Field), in which the objective was to address the social representations in the family context; concerning caring, as well as the burden it implies using a qualitative method. The corpus was built based on the analysis and interpretation gathered from families with mental illness members. There were 17 individual interviews, 13 group interviews and one family group of three generations, held regarding the clinical care of the family member. These interviews were held at three different hospitals in Bogota. The representation of "a family" constitutes the structuring of the meanings of family relationships that cope with mental illness built upon the social and historical life of its members. The three comprehensive categories were: a) Family in good times and bad times; b) mental illness in family interactions, and c) Care and burden. Socially speaking, mental illness can lead to dehumanization, in that it discriminates and stigmatizes, even within the family unit. Caring for a family member with mental illness comes about by hierarchical order, self assignation, and by institutionalization. This latter occurs due to lack of caregivers or because the family does not consider their home the best place to care for such a patient.


    Directory of Open Access Journals (Sweden)

    Siti Isfandari


    Full Text Available Priority of Indonesian health policy is maternal and child physical health. It is undeniable that physical health is very important in developing productive human beings. However, ignorance on child mental health can have an undesirable impact for both the child and the family. Early detection and appropriate treatment for the mentally vulnerable kid is then needed to help the child have a better future. The Household Health Survey (HHS 1995 included a Report Questionnaire for Children (RQC to detect the presence of mental emotional disturbance symptom. Analysis revealed that symptoms of mental disturbance for age 5-14 years was quite high: 102 in 1000 children. According to socio-demographic condition, the results showed no significant difference of mental disturbance symptoms between: rural vs. urban (98 vs. 108; household density <= 5 vs. > 5 (107 vs. 109; Java Bali vs. outer Java Bali (93 vs. 110 girls vs boys (95 vs. 109. Slight differences of mental disturbance symptoms was found between pre-puberty vs. puberty (88 vs. 116; low economic vs. high economic (119 vs. 87.It is expected that the results can provide inputs for developing a health policy to improve child health which includes mental health. 

  6. Media and mental illness: Relevance to India

    Directory of Open Access Journals (Sweden)

    S K Padhy


    Full Text Available Media has a complex interrelationship with mental illnesses. This narrative review takes a look at the various ways in which media and mental illnesses interact. Relevant scientific literature and electronic databases were searched, including Pubmed and GoogleScholar, to identify studies, viewpoints and recommendations using keywords related to media and mental illnesses. This review discusses both the positive and the negative portrayals of mental illnesses through the media. The portrayal of mental health professionals and psychiatric treatment is also discussed. The theories explaining the relationship of how media influences the attitudes and behavior are discussed. Media has also been suggested to be a risk factor for the genesis or exacerbation of mental illnesses like eating disorders and substance use disorders. The potential use of media to understand the psychopathology and plight of those with psychiatric disorders is referred to. The manner in which media can be used as a tool for change to reduce the stigma surrounding mental illnesses is explored.

  7. The National Mental Health Registry (NMHR). (United States)

    Aziz, A A; Salina, A A; Abdul Kadir, A B; Badiah, Y; Cheah, Y C; Nor Hayati, A; Ruzanna, Z Z; Sharifah Suziah, S M; Chee, K Y


    The National Mental Health Registry (NMHR) collects information about patients with mental disorder in Malaysia. This information allows us to estimate the incidence of selected mental disorders, and to evaluate risk factors and treatment in the country. The National Mental Health Registry (NMHR) presented its first report in 2004, a year after its establishment. The report focused on schizophrenia as a pioneer project for the National Mental Health Registry. The development of the registry has progressed with data collected from government-based facilities, the academia and the private sector. The 2003-2005 report was recently published and distributed. Since then the registry has progressed to include suicides and other mental illnesses such as depression. The NMHR Report 2003-2005 provides detailed information about the profile of persons with Schizophrenia who presented for the first time to various psychiatry and mental health providers throughout Malaysia. More detailed description regarding pharmacotherapy is reported and few cross tabulations done in an effort to provide better understanding and more clinically meaningful reports.

  8. Mental health nurses' contributions to community mental health care: An Australian study. (United States)

    Heslop, Brett; Wynaden, Dianne; Tohotoa, Jenny; Heslop, Karen


    Australian mental health policy is focused on providing mental health care in the community setting and community mental health teams provide services to clients in a shared model with primary care. The historical literature reports that community mental health nurses' experience high levels of stress and are often allocated the most complex and challenging clients managed by the team. Yet information on their specific roles remains limited. This paper reports on research conducted at one Australian public mental health service to identify the components of the community mental health nursing role and to quantify the time nurses spent in each component during the study period. Six focus groups were conducted with community mental health nurses to identify their perceived role within the team. Data analysis identified 18 components of which 10 were related to direct clinical contact with clients and eight covered administrative and care coordination activities. A data collection tool based on the findings of the focus groups was designed and nurses recorded workload data on the tool in 15-min intervals over a 4-week period. Seventeen nurses collected 1528 hours of data. Internal coordination of care was identified as the top workload item followed by clinical documentation and national data collection responsibilities supporting the complexity of the community mental health nursing role. The high rating attached to the internal coordination of care role demonstrates an important contribution that community mental health nurses make to the functioning of the team and the delivery of quality mental health care.

  9. Sport and physical activity for mental health

    CERN Document Server

    Carless, David


    With approximately 1 in 6 adults likely to experience a significant mental health problem at any one time (Office for National Statistics), research into effective interventions has never been more important. During the past decade there has been an increasing interest in the role that sport and physical activity can play in the treatment of mental health problems, and in mental health promotion. The benefits resulting from physiological changes during exercise are well documented, including improvement in mood and control of anxiety and depression. Research also suggests that socio-cultural a

  10. A New Priority for Mental Health



    Mental illness (especially depression and chronic anxiety) is the biggest single cause of misery in advanced countries. But only one quarter of those who are ill receive treatment. Mental health is crucial for wellbeing and there are modern evidence-based ways of treating mental health problems which have no net cost to the Exchequer. What are the most important factors affecting wellbeing in our society? And what low-cost ways do we have of improving wellbeing, when "all the money's gone"? T...

  11. The effect of exercise on mental health. (United States)

    Dunn, Andrea L; Jewell, Jennifer S


    Including exercise for the prevention and treatment of mental disorders is a promising area of research for exercise scientists since data indicate that many of these disorders are not treated at all, and there is a significant delay in treatment. This review provides an appraisal of the recent use of exercise to prevent and treat specific mental disorders and provides a recommended framework for future progress of this research. More research is needed to overcome methodological issues to demonstrate the efficacy and effectiveness of exercise and to integrate mental and physical healthcare for widespread dissemination.

  12. Mental health integration: normalizing team care. (United States)

    Reiss-Brennan, Brenda


    This article examines the impact of integrating mental health into primary health care. Mental Health Integration (MHI) within Intermountain Healthcare has changed the culture of primary health care by standardizing a team-based care process that includes mental health as a normal part of the routine medical encounter. Using a quantitative statistical analysis of qualitative reports (mixed methods study), the study reports on health outcomes associated with MHI for patients and staff. Researchers interviewed 59 patients and 50 staff to evaluate the impact of MHI on depression care. Patients receiving MHI reported an improved relationship with caregivers (P approach to improve outcomes.

  13. Electrotherapy and mental illness: then and now. (United States)

    Gilman, Sander L


    Today electrotherapy has reappeared as a therapy of choice for the treatment of depression and other forms of mental illness. It had de facto vanished from allopathic medicine from the 1920s to the end of the century. The debates about electrotherapy mirror the question of whether mental illness was somatic and to be treated by somatic means or psychological to be treated with psychotherapy. Sigmund Freud's move from an advocate to an opponent of electrotherapy is exemplary for a shift in attitude and the decline of electrotherapy. With the re-somaticization of mental illness over the past decades has come the reappearance of somatic therapies such as electrotherapy.


    Directory of Open Access Journals (Sweden)

    Nadeem Ahmad


    Full Text Available The mental health of the child affects his physical health and the learning process. The present study was conducted to study the health status and etiological factors among 58 mentally challenged children in school for mentally challenged at Sangamner. Majority of mentally challenged children (68.0% were in 5-9 years age group. Most of them had moderate retardation. (43.0% In majority of children (70.68%no clinical syndrome was present. Most common clinical syndrome was Down’s syndrome (17.23%,followed by Fragile X syndrome (6.89%. More than sixty percent children were off springs of consanguineous marriages. Idiopathic causes (63.8% followed by genetic causes (29.31% were common etiological factor responsible for mental retardation. Mental handicap can be prevented by genetic counseling.

  15. Disease: H00667 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00667 Woolly hair, including: Autosomal-dominant woolly hair (ADWH); Autosomal-rec...essive woolly hair (ARWH); Autosomal-recessive woolly hair with or without hypotrichosis Woolly hair (WH) is...autosomal dominant and autosomal recessive manner. Autosomal recessive woolly hai..., Wajid M, Petukhova L, Kurban M, Christiano AM Autosomal-dominant woolly hair re

  16. Mass Mentality, Culture Industry, Fascism

    Directory of Open Access Journals (Sweden)

    Saladdin Said Ahmed


    Full Text Available Some fashionable leftist movements and populist intellectuals habitually blame the sources of information for public ignorance about the miserable state of the world. It could be argued, however, that the masses are ignorant because they prefer ignorance. A mass individual is politically apathetic and intellectually lazy. As a result, even when huge amounts of information are available, which is the case in this epoch, the masses insist on choosing ignorance. It is true that there is not enough information about what has happened in a place such as Darfur, but the masses choose not to access even the amount of information that is available. The great majority of people in China, Iran, and America, despite the fact that they have varying amounts of access to various types of "knowledge," still tend to be misinformed. It seems that a mass individual is curious only about what directly affects his/her own personal life. I will explore the connection between mass mentality and the culture industry in order to capture the essential role of the former in the latter. I will also argue that a mass individual is the source of fascism although fascism as a phenomenon needs a mass culture in which to flourish.

  17. Interconnected or disconnected? Promotion of mental health and prevention of mental disorder in the digital age. (United States)

    Hayes, Joseph F; Maughan, Daniel L; Grant-Peterkin, Hugh


    To date there have been few peer-reviewed studies on the feasibility, acceptability and effectiveness of digital technologies for mental health promotion and disorder prevention. Any evaluation of these evolving technologies is complicated by a lack of understanding about the specific risks and possible benefits of the many forms of internet use on mental health. To adequately meet the mental health needs of today's society, psychiatry must engage in rigorous assessment of the impact of digital technologies.

  18. Team learning: building shared mental models

    NARCIS (Netherlands)

    Van den Bossche, Piet; Gijselaers, Wim; Segers, Mien; Woltjers, Geert; Kirschner, Paul A.


    Van den Bossche, P., Gijselaers, W., Segers, M., Woltjer, G., & Kirschner, P. A. (2011). Team learning: Building shared mental models. Instructional Science, 39, 283-301. doi:10.1007/s11251-010-9128-3.

  19. Video Tape and the Mentally Retarded (United States)

    Weisbord, H. F.


    Three uses of video tape recordings with the mentally retarded; discussed briefly are staff training or teacher education, parental involvement in the child's education, and therapeutic uses by psychiatrists and psychologists. (CB)

  20. Literature Review on Bilingual Mental Lexicon

    Institute of Scientific and Technical Information of China (English)

    刘佳佳; 徐慧洁


    In the past 50 years, psychologists and linguists have put forward various theoretical hypothesis as to bilingual conceptual representations.This paper provides a review of theories concerning bihngual mental lexicon.