WorldWideScience

Sample records for nonsense mutation-mediated disorders

  1. The sound of nonsense

    DEFF Research Database (Denmark)

    Borcak, Lea Maria Lucas Wierød

    2017-01-01

    not explicated, probably due to disciplinary borders. This article juxtaposes different observations about nonsense for the purpose of illuminating their mutual concordance and contributing to a systematic and comprehensible framework for understanding types and functions of verbal nonsense in songs....

  2. Shuffled Cards, Messy Desks, and Disorderly Dorm Rooms - Examples of Entropy Increase? Nonsense!

    Science.gov (United States)

    Lambert, Frank L.

    1999-10-01

    The order of presentation in this article is unusual; its conclusion is first. This is done because the title entails text and lecture examples so familiar to all teachers that most may find a preliminary discussion redundant. Conclusion The dealer shuffling cards in Monte Carlo or Las Vegas, the professor who mixes the papers and books on a desk, the student who tosses clothing about his or her room, the fuel for the huge cranes and trucks that would be necessary to move the nonbonded stones of the Great Pyramid of Cheops all across Egypteach undergoes physical, thermodynamic entropy increase in these specific processes. The thermodynamic entropy change from human-defined order to disorder in the giant Egyptian stones themselves, in the clothing and books in a room or papers on a desk, and in the millions of cards in the world's casinos is precisely the same: Zero. K. G. Denbigh succinctly summarizes the case against identifying changes in position in one macro object or in a group with physical entropy change (1): If one wishes to substantiate a claim or a guess that some particular process involves a change of thermodynamic or statistical entropy, one should ask oneself whether there exists a reversible heat effect, or a change in the number of accessible energy eigenstates, pertaining to the process in question. If not, there has been no change of physical entropy (even though there may have been some change in our "information"). Thus, simply changing the location of everyday macro objects from an arrangement that we commonly judge as orderly (relatively singular) to one that appears disorderly (relatively probable) is a "zero change" in the thermodynamic entropy of the objects because the number of accessible energetic microstates in any of them has not been changed. Finally, although it may appear obvious, a collection of ordinary macro things does not constitute a thermodynamic system as does a group of microparticles. The crucial difference is that such

  3. The sound of nonsense

    DEFF Research Database (Denmark)

    Borcak, Lea Maria Lucas Wierød

    2017-01-01

    : music, text, the visual, the aural etc. It has been pointed out by several musicologists that content analysis of texts, despite having had a long historical tradition, is nonetheless insufficient or even downright misleading as a methodological approach to interpreting songs. The extensive use......Nonsense words in songs challenge the common assumption that song meaning resides in song texts. Songs containing verbal nonsense thus make evident that meaning cannot be deduced from one element (e.g. text), but rather emerges as a constant negotiation between the different medialities involved...

  4. Sense Meets Nonsense

    DEFF Research Database (Denmark)

    Christiansen, Thomas Ulrich; Henrichsen, Peter Juel

    2012-01-01

    for investigating the relationship between early stages of the speech perceptual process and later stages. We present our considerations involved in preparing the experimental set-up, producing the anechoic recordings, compiling the data, and exploring the materials in linguistic research. We report on a small......In this paper, we present the newly established Danish speech corpus PiTu. The corpus consists of recordings of 28 native Danish talkers (14 female and 14 male) each reproducing (i) a series of nonsense syllables, and (ii) a set of authentic natural language sentences. The speech corpus is tailored...... pilot experiment demonstrating how PiTu and similar speech corpora can be used in studies of prosody as a function of semantic content. The experiment addresses the issue of whether the governing principles of Danish prosody assignment is mainly talker-specific or mainly content-typical (under...

  5. Death, dignity, and moral nonsense.

    Science.gov (United States)

    Pullman, Daryl

    2004-01-01

    Although the concept of human dignity is widely invoked in discussions regarding end-of-life decision making, the content of the notion is ambiguous. Such ambiguity has led some to conclude that human dignity is a redundant or even useless concept that we would be better off without. This paper argues, to the contrary, that the concept of human dignity is indispensable to moral discourse. Far from dispensing with human dignity, we must work to clarify the concept. The paper outlines two distinct but related conceptions of dignity that are often conflated in contemporary moral discourse. These conceptions are labelled "basic dignity" and "personal dignity", respectively. It is argued that basic dignity functions as a universal meaning constraint on moral discourse in general. Hence, to dispense with the notion could reduce us to speaking moral nonsense. Throughout the discussion, some implications for our understanding of end-of-life decision making are explored.

  6. Novel LMF1 Nonsense Mutation in a Patient with Severe Hypertriglyceridemia

    OpenAIRE

    Cefalù, Angelo B.; Noto, Davide; Arpi, Maria Luisa; Yin, Fen; Spina, Rossella; Hilden, Hannele; Barbagallo, Carlo M.; Carroccio, Antonio; Tarugi, Patrizia; Squatrito, Sebastiano; Vigneri, Riccardo; Taskinen, Marja-Riitta; Péterfy, Miklós; Averna, Maurizio R.

    2009-01-01

    Context: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X).

  7. Messenger RNA surveillance: neutralizing natural nonsense

    DEFF Research Database (Denmark)

    Weischelfeldt, Joachim Lütken; Lykke-Andersen, Jens; Porse, Bo

    2005-01-01

    Messenger RNA transcripts that contain premature stop codons are degraded by a process termed nonsense-mediated mRNA decay (NMD). Although previously thought of as a pathway that rids the cell of non-functional mRNAs arising from mutations and processing errors, new research suggests a more general...

  8. Splice, insertion-deletion and nonsense mutations that perturb the phenylalanine hydroxylase transcript cause phenylketonuria in India.

    Science.gov (United States)

    Bashyam, Murali D; Chaudhary, Ajay K; Kiran, Manjari; Nagarajaram, Hampapathalu A; Devi, Radha Rama; Ranganath, Prajnya; Dalal, Ashwin; Bashyam, Leena; Gupta, Neerja; Kabra, Madhulika; Muranjan, Mamta; Puri, Ratna D; Verma, Ishwar C; Nampoothiri, Sheela; Kadandale, Jayarama S

    2014-03-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by mutational inactivation of the phenylalanine hydroxylase (PAH) gene. Missense mutations are the most common PAH mutation type detected in PKU patients worldwide. We performed PAH mutation analysis in 27 suspected Indian PKU families (including 7 from our previous study) followed by structure and function analysis of specific missense and splice/insertion-deletion/nonsense mutations, respectively. Of the 27 families, disease-causing mutations were detected in 25. A total of 20 different mutations were identified of which 7 "unique" mutations accounted for 13 of 25 mutation positive families. The unique mutations detected exclusively in Indian PKU patients included three recurrent mutations detected in three families each. The 20 mutations included only 5 missense mutations in addition to 5 splice, 4 each nonsense and insertion-deletion mutations, a silent variant in coding region and a 3'UTR mutation. One deletion and two nonsense mutations were characterized to confirm significant reduction in mutant transcript levels possibly through activation of nonsense mediated decay. All missense mutations affected conserved amino acid residues and sequence and structure analysis suggested significant perturbations in the enzyme activity of respective mutant proteins. This is probably the first report of identification of a significantly low proportion of missense PAH mutations from PKU families and together with the presence of a high proportion of splice, insertion-deletion, and nonsense mutations, points to a unique PAH mutation profile in Indian PKU patients. © 2013 Wiley Periodicals, Inc.

  9. An UPF3-based nonsense-mediated decay in Paramecium.

    Science.gov (United States)

    Contreras, Julia; Begley, Victoria; Macias, Sandra; Villalobo, Eduardo

    2014-12-01

    Nonsense-mediated decay recognises mRNAs containing premature termination codons. One of its components, UPF3, is a molecular link bridging through its binding to the exon junction complex nonsense-mediated decay and splicing. In protists UPF3 has not been identified yet. We report that Paramecium tetraurelia bears an UPF3 gene and that it has a role in nonsense-mediated decay. Interestingly, the identified UPF3 has not conserved the essential amino acids required to bind the exon junction complex. Though, our data indicates that this ciliate bears genes coding for core proteins of the exon junction complex. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Detecting nonsense for Chinese comments based on logistic regression

    Science.gov (United States)

    Zhuolin, Ren; Guang, Chen; Shu, Chen

    2016-07-01

    To understand cyber citizens' opinion accurately from Chinese news comments, the clear definition on nonsense is present, and a detection model based on logistic regression (LR) is proposed. The detection of nonsense can be treated as a binary-classification problem. Besides of traditional lexical features, we propose three kinds of features in terms of emotion, structure and relevance. By these features, we train an LR model and demonstrate its effect in understanding Chinese news comments. We find that each of proposed features can significantly promote the result. In our experiments, we achieve a prediction accuracy of 84.3% which improves the baseline 77.3% by 7%.

  11. The no-nonsense guide to project management

    CERN Document Server

    Allan, Barbara

    2017-01-01

    This book provides a 'no-nonsense' guide to project management which will enable library and information professionals to lead or take part in a wide range of projects from large-scale multi-organisation complex projects through to relatively simple local ones.

  12. FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome

    Directory of Open Access Journals (Sweden)

    Dahl Niklas

    2011-03-01

    Full Text Available Abstract Background Ichthyosis Prematurity Syndrome (IPS is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4 and a specific reduction in the incorporation of very long chain fatty acids (VLCFA into cellular lipids. Findings We screened probands from five families segregating IPS for mutations in the FATP4 gene. Four probands were compound heterozygous for four different mutations of which three are novel. Four patients were heterozygous and one patient homozygous for the previously reported non-sense mutation p.C168X (c.504c > a. All patients had clinical characteristics of IPS and a similar clinical course. Conclusions Missense mutations and non-sense mutations in FATP4 are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function. The results broaden the mutational spectrum in FATP4 associated with IPS for molecular diagnosis of and further functional analysis of FATP4.

  13. Recurrent hyperparathyroidism and a novel nonsense mutation in a patient with hyperparathyriodism-jaw tumor syndrome.

    Science.gov (United States)

    Abdulla, Amer G; O'Leary, Erin M; Isorena, Jennifer P; Diaz, Miguel Fernando Palma; Yeh, Michael W

    2013-01-01

    To present the case of a hyperparathyroidism-jaw tumor (HPT-JT) patient with a novel nonsense mutation of the CDC73 gene. We present the case of a patient with a history of three prior maxillectomies and two prior parathyroidectomies who presented with recurrent primary hyperparathyroidism (PHPT). We also briefly review the literature pertaining to HPT-JT. Genetic analysis revealed a novel nonsense mutation (c.85G>T; pGlu29) in exon 1 of CDC73. The patient's son underwent genetic testing for a CDC73 mutation and was found to be negative. HPT-JT is a rare condition characterized by PHPT and benign tumors of the mandible and maxilla. Up to 15% of HPT-JT patients with PHPT have parathyroid carcinoma. HPT-JT is associated with an inactivating mutation of CDC73, a gene that codes for the tumor suppressor protein parafibromin. This report expands our understanding of the genetics underlying this rare disorder and emphasizes the importance of early detection in order to prevent hypercalcemic complications such as parathyroid carcinoma.

  14. Waardenburg syndrome type II in a Chinese patient caused by a novel nonsense mutation in the SOX10 gene.

    Science.gov (United States)

    Ma, Jing; Zhang, Tie-Song; Lin, Ken; Sun, Hao; Jiang, Hong-Chao; Yang, Yan-Li; Low, Fan; Gao, Ying-Qin; Ruan, Biao

    2016-06-01

    Waardenburg syndrome is a congenital genetic disorder. It is the most common type of syndromic hearing impairment with highly genetic heterogeneity and proved to be related by 6 genes as follows: PAX3, MITF, SNAI2, EDN3, EDNRB and SOX10. This article aims to identify the genetic causes of a Chinese WS child patient. A Chinese WS child was collected for clinical data collection by questionnaire survey. DNA samples of proband and his parents were extracted from peripheral blood samples. Six candidate genes were sequenced by the Trusight One sequencing panel on the illumina NextSeq 500 platform. A novel nonsense heterozygous mutation was found in the coding region of exon 2 in the SOX10 gene of proband. The novel nonsense heterozygous mutation could cause the replacement of the 55th lysine codon by stop codon (484T > C, C142R) and further more possibly cause terminating the protein translation in advance. However, both proband's parents had no mutation of genes above mentioned. The gene mutation of SOX10 [NM_006941.3 c.163A > T] is a novel nonsense mutation. No record of this mutation has been found in dbSNP, HGMD, 1000 Genomes Project, ClinVar and ESP6500 databases. It meets the condition of PS2 of strong evidence in 2015 ACMG Standards and Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I

    Directory of Open Access Journals (Sweden)

    Kairong Li

    2016-07-01

    Full Text Available Neurofibromatosis type 1 (NF1 is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681* and a missense mutation (c.2542G>C; p.Gly848Arg. The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1Arg681* and missense NF1Gly848Arg mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1Gly848Arg mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1Arg681* mutation are not viable. Mice with one Nf1Arg681* allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf14F/Arg681*; DhhCre display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1.

  16. Immunodeficiency associated with a nonsense mutation of IKBKB

    DEFF Research Database (Denmark)

    Nielsen, Christian; Jakobsen, Marianne A; Larsen, Martin Jakob

    2014-01-01

    We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory insufficie......We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory...... no explanation before whole exome sequencing revealed a novel mutation abrogating signaling through the canonical NF-κB pathway....

  17. Novel heterozygous nonsense mutation of the OPTN gene segregating in a Danish family with ALS

    DEFF Research Database (Denmark)

    Tümer, Zeynep; Bertelsen, Birgitte; Gredal, Ole

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. About 10% of ALS cases are familial (FALS) and the genetic defect is known only in approximately 20%-30% of these cases. The most common genetic cause of ALS is SOD1 (superoxide dismutase 1) mutation. Very recently......, mutations of the optineurin gene (OPTN), which is involved in open-angle glaucoma, were identified in 3 Japanese patients/families with ALS, and subsequently in a few FALS patients of European descent. We found a heterozygous nonsense mutation (c.493C>T, p.Gln165X, exon 6) in the OPTN gene in a Danish...... patient with ALS, and the mutation segregated from his affected father. The p.Gln165X mutation could not be detected in 1070 healthy Danish controls, in 1000 Danish individuals with metabolic phenotypes or in 64 sporadic ALS (SALS) cases. The p.Gln165X mutation described in this study is the first...

  18. Culture-specific delusions. Sense and nonsense in cultural context.

    Science.gov (United States)

    Gaines, A D

    1995-06-01

    It can be said that a definition of delusions requires the invocation of cultural understandings, standards of acceptability, as well as conceptions of reality and the forces that animate it. For these reasons, the determination of delusional or normative ideation can only be effected properly within particular cultural contexts. The cross-cultural record suggests that it is difficult to separate the delusional from the cultural; a belief that is patterened and culturally specific is, by definition a cultural, not a delusional belief. One must rely upon particular, relevant local cultural understandings to ascertain when the bounds of culture have been transgressed and meaning has given way to unshareable nonsense.

  19. Heidegger: Sense-Nonsense Dualism of Man in Technology Dimensions

    OpenAIRE

    Nathalia Andrea Álvarez

    2008-01-01

    This article tries to analyze the ontological-existential compromise that man acquires when using new technologies, in the light of theHeideggerian’ proposal. This compromise means, on the one hand, theresponsibility of forgetting the self in technology, which immerses man in a non-sense; and on the other, the will to open himself to the recognition of the ways in which his “being-in-the-world” manifests. To this end, the perils of technological “instrumentalization” will be presented, based ...

  20. Nonsense mutation in the glycoprotein Ibα coding sequence associated with Bernard-Soulier syndrome

    International Nuclear Information System (INIS)

    Ware, J.; Russell, S.R.; Vicente, V.; Scharf, R.E.; Tomer, A.; McMillian, R.; Ruggeri, Z.M.

    1990-01-01

    Three distinct gene products, the α and β chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. The authors have analyzed the molecular basis of the disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ibα but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ibα, which by lacking half of the sequence on the carboxyl-terminal side, including the transmembrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ibα allele. Nonsense mutation and truncated GP Ibα polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ibα alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome

  1. Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients.

    Science.gov (United States)

    Yang, Shu-Zhi; Cao, Ju-Yang; Zhang, Rui-Ning; Liu, Li-Xian; Liu, Xin; Zhang, Xin; Kang, Dong-Yang; Li, Mei; Han, Dong-Yi; Yuan, Hui-Jun; Yang, Wei-Yan

    2007-01-05

    Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.

  2. Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

    Science.gov (United States)

    Bashyam, Murali D

    2009-01-01

    Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

  3. A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

    Science.gov (United States)

    Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

    2010-12-08

    Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

  4. A novel GATA3 nonsense mutation in a newly diagnosed adult patient of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

    Science.gov (United States)

    Nanba, Kazutaka; Usui, Takeshi; Nakamura, Michikazu; Toyota, Yuko; Hirota, Keisho; Tamanaha, Tamiko; Kawashima, Sachiko-Tsukamoto; Nakao, Kanako; Yuno, Akiko; Tagami, Tetsuya; Naruse, Mitsuhide; Shimatsu, Akira

    2013-01-01

    Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by a GATA3 gene mutation. Here we report a novel mutation of GATA3 in a patient diagnosed with HDR syndrome at the age of 58 with extensive intracranial calcification. A 58-year-old Japanese man showed severe hypocalcemia and marked calcification in the basal ganglia, cerebellum, deep white matter, and gray-white junction on computed tomography (CT). The serum intact parathyroid hormone level was relatively low against low serum calcium concentration. The patient had been diagnosed with bilateral sensorineural deafness in childhood and had a family history of hearing disorders. Imaging studies revealed no renal anomalies. The patient was diagnosed with HDR syndrome, and genetic testing was performed. Genetic analysis of GATA3 showed a novel nonsense mutation at codon 198 (S198X) in exon 3. The S198X mutation leads to a loss of two zinc finger deoxyribonucleic acid (DNA) binding domains and is considered to be responsible for HDR syndrome. We identified a novel nonsense mutation of GATA3 in an adult patient with HDR syndrome who showed extensive intracranial calcification.

  5. Nonsense mutants in the bacteriophage T4D v gene

    Energy Technology Data Exchange (ETDEWEB)

    Minderhout, L van; Grimbergen, J; Groot, B de [Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese; Cohen (J.A.) Instituut voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

    1975-09-01

    Ten UV-sensitive mutants of T4D with the v phenotype were isolated. Of these ten mutants, two are amber and two opal. In UV curves and in photoreactivation and multiplicity reactivation experiments the nonsense mutants show the v phenotype in su/sup -/ hosts and almost the T4/sup +/ phenotype in su/sup +/ hosts. The mutations are located between rl and e and are alleles of v/sub 1/. In crosses with irradiated and non-irradiated phages the recombinant frequency is not reduced by uvs5. Amber uvs5 propagated in CR63 su/sup +/ is with B su/sup -/ just as sensitive to UV as uvs5 propagated in B su/sup -/, which permits the conclusion that the capsid of T4 phage particles does not contain the v gene product.

  6. Nonsense,Nonscience,and Science from Creationism to Aliens

    CERN Document Server

    Krauss, L

    1997-01-01

    In 1996, U.S. presidential candidate Patrick Buchanan announced on national television that he was not descended from monkeys, and moreover, he thought children should not be taught this. Yet, not a single reporter questioned him on this remarkable statement, in spite of detailed questions on his economic policies. For some reason, the media is hesitant, when referring to scientific issues, to indicate that in certain issues there is no debate, namely there is simply a right answer and a wrong answer. This is so in spite of the fact that science provides, perhaps more than anything else, a set of techniques for distinguishing nonsense. I will talk about the historical context of this issue, the dangers it imposes, and provide examples from the press, as well as clips from television and movies, of mixing up science and fiction, as well as describe ways to avoid this.

  7. Heidegger: Sense-Nonsense Dualism of Man in Technology Dimensions

    Directory of Open Access Journals (Sweden)

    Nathalia Andrea Álvarez

    2008-12-01

    Full Text Available This article tries to analyze the ontological-existential compromise that man acquires when using new technologies, in the light of theHeideggerian’ proposal. This compromise means, on the one hand, theresponsibility of forgetting the self in technology, which immerses man in a non-sense; and on the other, the will to open himself to the recognition of the ways in which his “being-in-the-world” manifests. To this end, the perils of technological “instrumentalization” will be presented, based upon the Heideggerian explanation about the essence of technology. We will present the Heideggerian concepts of anxiety1 and nothingness concepts, with which we will try to conduct the postmodern man towards the encounter with his original sense.

  8. A nonsense mutation in FMR1 causing fragile X syndrome

    DEFF Research Database (Denmark)

    Grønskov, Karen; Brøndum-Nielsen, Karen; Dedic, Alma

    2011-01-01

    Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5'UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent....... Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense...... mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should...

  9. Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations.

    Science.gov (United States)

    Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Wolfrum, Uwe

    2014-09-01

    The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30-50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the

  10. Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.

    Science.gov (United States)

    Nguyen, Andrew D; Nguyen, Thi A; Zhang, Jiasheng; Devireddy, Swathi; Zhou, Ping; Karydas, Anna M; Xu, Xialian; Miller, Bruce L; Rigo, Frank; Ferguson, Shawn M; Huang, Eric J; Walther, Tobias C; Farese, Robert V

    2018-03-20

    Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized Grn R493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous Grn R493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macrophages, excessive grooming behavior, and reduced survival. Inhibition of nonsense-mediated mRNA decay (NMD) by genetic, pharmacological, or antisense oligonucleotide-based approaches showed that NMD contributes to the reduced mRNA levels in Grn R493X mice and cell lines and in fibroblasts from patients containing the GRN R493X mutation. Moreover, the expressed truncated R493X mutant protein was functional in several assays in progranulin-deficient cells. Together, these findings establish a murine model for in vivo testing of NMD inhibition or other therapies as potential approaches for treating progranulin deficiency caused by the R493X mutation. Copyright © 2018 the Author(s). Published by PNAS.

  11. Molecular Diagnosis of Analbuminemia: A New Case Caused by a Nonsense Mutation in the Albumin Gene

    Directory of Open Access Journals (Sweden)

    Lorenzo Minchiotti

    2011-10-01

    Full Text Available Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB. We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB gene, carried out by single-strand conformational polymorphism (SSCP, heteroduplex analysis (HA, and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23–c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis.

  12. Molecular diagnosis of analbuminemia: a new case caused by a nonsense mutation in the albumin gene.

    Science.gov (United States)

    Dagnino, Monica; Caridi, Gianluca; Haenni, Ueli; Duss, Adrian; Aregger, Fabienne; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo

    2011-01-01

    Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB) gene, carried out by single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23-c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis.

  13. Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome.

    Science.gov (United States)

    Bodoor, Khaldon; Batiha, Osama; Abu-Awad, Ayman; Al-Sarihin, Khaldon; Ziad, Haya; Jarun, Yousef; Abu-Sheikha, Aya; Abu Jalboush, Sara; Alibrahim, Khoulod S

    2016-09-01

    Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder characterized by the presentation of early onset type I diabetes mellitus and optic atrophy with later onset diabetes insipidus and deafness. WFS1 gene was identified on chromosome 4p16.1 as the gene responsible for WS disease given that most of the WS patients were found to carry mutations in this gene. This study was carried out to investigate the molecular spectrum of WFS1 gene in Jordanian families. Molecular and clinical characterization was performed on five WS patients from two unrelated Jordanian families. Our data indicated that WS patients of the first family harbored two deletion mutations (V415del and F247fs) located in exon 8 and exon 7 respectively, with a compound heterozygous pattern of inheritance; while in the second family, we identified a novel nonsense mutation (W185X) located in exon 5 in the N-terminal cytoplasmic domain with a homozygous pattern of inheritance. This mutation can be considered as loss of function mutation since the resulting truncated protein lost both the transmembrane domain and the C-terminal domain. Additionally, the W185X mutation lies within the CaM binding domain in wolframin protein which is thought to have a role in the regulation of wolframin function in response to calcium levels.

  14. Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A.

    Science.gov (United States)

    Krunic, Aleksandar L; Stone, Kristina L; Simpson, Michael A; McGrath, John A

    2013-01-01

    Acral peeling skin syndrome (APSS) is a clinically and genetically heterogeneous disorder. We used whole-exome sequencing to identify the molecular basis of APSS in a consanguineous Jordanian-American pedigree. We identified a homozygous nonsense mutation (p.Lys22X) in the CSTA gene, encoding cystatin A, that was confirmed using Sanger sequencing. Cystatin A is a protease inhibitor found in the cornified cell envelope, and loss-of-function mutations have previously been reported in two cases of exfoliative ichthyosis. Our study expands the molecular pathology of APSS and demonstrates the value of next-generation sequencing in the genetic characterization of inherited skin diseases. © 2013 Wiley Periodicals, Inc.

  15. Efficient generation of mutations mediated by CRISPR/Cas9 in the hairy root transformation system of Brassica carinata.

    Science.gov (United States)

    Kirchner, Thomas W; Niehaus, Markus; Debener, Thomas; Schenk, Manfred K; Herde, Marco

    2017-01-01

    A protocol for the induction of site-directed deletions and insertions in the genome of Brassica carinata with CRISPR is described. The construct containing the Cas9 nuclease and the guide RNA (gRNA) was delivered by the hairy root transformation technique, and a successful transformation was monitored by GFP fluorescence. PAGE analysis of an amplified region, presumably containing the deletions and insertions, demonstrated up to seven different indels in one transgenic root and in all analyzed roots a wildtype allele of the modified gene was not detectable. Interestingly, many of these mutations consisted of relatively large indels with up to 112 bp. The exact size of the deletions was determined to allow an estimation whether the targeted gene was not functional due to a considerable deletion or a frame shift within the open reading frame. This allowed a direct phenotypic assessment of the previously characterized roots and, in fact, deletions in FASCICLIN-LIKE ARABINOGALACTAN PROTEIN 1 (BcFLA1)-a gene with an expression pattern consistent with a role in root hair architecture-resulted in shorter root hairs compared to control roots ectopically expressing an allele of the gene that cannot be targeted by the gRNA in parallel to the CRISPR construct. As an additional line of evidence, we monitored BcFLA1 expression with qPCR and detected a significant reduction of the transcript in roots with an active CRISPR construct compared to the control, although residual amounts of the transcript were detected, possibly due to inefficient nonsense-mediated mRNA decay. Additionally, the presence of deletions and insertions were verified by Sanger sequencing of the respective amplicons. In summary we demonstrate the successful application of CRISPR/Cas9 in hairy roots of B. carinata, the proof of its effectiveness and its effect on the root hair phenotype. This study paves the way for experimental strategies involving the phenotypic assessment of gene lesions by CRISPR which

  16. Efficient generation of mutations mediated by CRISPR/Cas9 in the hairy root transformation system of Brassica carinata.

    Directory of Open Access Journals (Sweden)

    Thomas W Kirchner

    Full Text Available A protocol for the induction of site-directed deletions and insertions in the genome of Brassica carinata with CRISPR is described. The construct containing the Cas9 nuclease and the guide RNA (gRNA was delivered by the hairy root transformation technique, and a successful transformation was monitored by GFP fluorescence. PAGE analysis of an amplified region, presumably containing the deletions and insertions, demonstrated up to seven different indels in one transgenic root and in all analyzed roots a wildtype allele of the modified gene was not detectable. Interestingly, many of these mutations consisted of relatively large indels with up to 112 bp. The exact size of the deletions was determined to allow an estimation whether the targeted gene was not functional due to a considerable deletion or a frame shift within the open reading frame. This allowed a direct phenotypic assessment of the previously characterized roots and, in fact, deletions in FASCICLIN-LIKE ARABINOGALACTAN PROTEIN 1 (BcFLA1-a gene with an expression pattern consistent with a role in root hair architecture-resulted in shorter root hairs compared to control roots ectopically expressing an allele of the gene that cannot be targeted by the gRNA in parallel to the CRISPR construct. As an additional line of evidence, we monitored BcFLA1 expression with qPCR and detected a significant reduction of the transcript in roots with an active CRISPR construct compared to the control, although residual amounts of the transcript were detected, possibly due to inefficient nonsense-mediated mRNA decay. Additionally, the presence of deletions and insertions were verified by Sanger sequencing of the respective amplicons. In summary we demonstrate the successful application of CRISPR/Cas9 in hairy roots of B. carinata, the proof of its effectiveness and its effect on the root hair phenotype. This study paves the way for experimental strategies involving the phenotypic assessment of gene lesions

  17. A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

    Science.gov (United States)

    Khateb, Samer; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Ayuso, Carmen; Koenekoop, Robert K; Laxer, Uri; Gross, Menachem; Banin, Eyal; Sharon, Dror

    2014-07-01

    Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2012-11-01

    Full Text Available Nonsense-mediated mRNA decay (NMD is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The nine most common genotypes, each with an incidence rate of 1.5% or over, and together accounting for 80% of genotype frequencies, underwent statistical analysis. Genotype prevalence was calculated within the overall group. Results are expressed as proportions with 95% confidence intervals; P≤0.05 was considered statistically significant. A binomial distribution was assumed for each group; z-tests were used to compare genotype frequencies observed in the patient group with frequencies in the affected fetus group. In the absence of selecting factors, prevalence of these two genotypes was compared between a cohort of 568 β-thalassemia patients (PTS and 577 affected fetuses (FOET detected during the same period. IVS1,nt110/cd39 was significantly more prevalent in FOET than PTS (P<0.0001, while there was no significant difference in prevalence of cd39/cd39 in FOET compared with PTS (P=0.524. These results suggest a cd39 genotype NMD mechanism may be associated with improved clinical outcomes in thalassemia major. 无义介导的mRNA 降解(NMD) 是一种预防非功能性蛋白质合成的监控系统。在β地中海贫血中,NMD可能对临床结果有影响。第一次出现的过早终止密码子(PTC)为β珠蛋白cd39突变;若为纯合

  19. Notes on a Bit of Psychological Nonsense: "Race Differences in Intelligence"

    Science.gov (United States)

    Schoenfeld, William N.

    1974-01-01

    The issue of race differences in intelligence, especially with respect to American black and white populations, is adjudged to be "nonsensical" in terms of the framing of the question, the populations sampled, the testing instruments utilized, and the concept of "intelligence" postulated. (Author/EH)

  20. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    NARCIS (Netherlands)

    Hoischen, Alexander; van Bon, Bregje W. M.; Rodríguez-Santiago, Benjamín; Gilissen, Christian; Vissers, Lisenka E. L. M.; de Vries, Petra; Janssen, Irene; van Lier, Bart; Hastings, Rob; Smithson, Sarah F.; Newbury-Ecob, Ruth; Kjaergaard, Susanne; Goodship, Judith; McGowan, Ruth; Bartholdi, Deborah; Rauch, Anita; Peippo, Maarit; Cobben, Jan M.; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Veltman, Joris A.; Brunner, Han G.; de Vries, Bert B. B. A.

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is

  1. Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity

    NARCIS (Netherlands)

    Josifova, Dragana J.; Monroe, Glen R.; Tessadori, Federico; de Graaff, Esther; van der Zwaag, Bert; Mehta, Sarju G.; Harakalova, Magdalena; Duran, Karen J.; Savelberg, Sanne M. C.; Nijman, Isaäc J.; Jungbluth, Heinz; Hoogenraad, Casper C.; Bakkers, Jeroen; Knoers, Nine V.; Firth, Helen V.; Beales, Philip L.; van Haaften, Gijs; van Haelst, Mieke M.

    2016-01-01

    We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally

  2. First de novo ANK3 nonsense mutation in a boy with intellectual disability, speech impairment and autistic features.

    Science.gov (United States)

    Kloth, Katja; Denecke, Jonas; Hempel, Maja; Johannsen, Jessika; Strom, Tim M; Kubisch, Christian; Lessel, Davor

    2017-09-01

    Ankyrin-G, encoded by ANK3, plays an important role in neurodevelopment and neuronal function. There are multiple isoforms of Ankyrin-G resulting in differential tissue expression and function. Heterozygous missense mutations in ANK3 have been associated with autism spectrum disorder. Further, in three siblings a homozygous frameshift mutation affecting only the longest isoform and a patient with a balanced translocation disrupting all isoforms were documented. The latter four patients were affected by a variable degree of intellectual disability, attention deficit hyperactivity disorder and autism. Here, we report on a boy with speech impairment, intellectual disability, autistic features, macrocephaly, macrosomia, chronic hunger and an altered sleeping pattern. By trio-whole-exome sequencing, we identified the first de novo nonsense mutation affecting all ANK3 transcripts. Thus, our data expand the phenotype of ANK3-associated diseases and suggest an isoform-based, phenotypic continuum between dominant and recessive ANK3-associated pathologies. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Alternative Polyadenylation and Nonsense-Mediated Decay Coordinately Regulate the Human HFE mRNA Levels

    Science.gov (United States)

    Martins, Rute; Proença, Daniela; Silva, Bruno; Barbosa, Cristina; Silva, Ana Luísa; Faustino, Paula; Romão, Luísa

    2012-01-01

    Nonsense-mediated decay (NMD) is an mRNA surveillance pathway that selectively recognizes and degrades defective mRNAs carrying premature translation-termination codons. However, several studies have shown that NMD also targets physiological transcripts that encode full-length proteins, modulating their expression. Indeed, some features of physiological mRNAs can render them NMD-sensitive. Human HFE is a MHC class I protein mainly expressed in the liver that, when mutated, can cause hereditary hemochromatosis, a common genetic disorder of iron metabolism. The HFE gene structure comprises seven exons; although the sixth exon is 1056 base pairs (bp) long, only the first 41 bp encode for amino acids. Thus, the remaining downstream 1015 bp sequence corresponds to the HFE 3′ untranslated region (UTR), along with exon seven. Therefore, this 3′ UTR encompasses an exon/exon junction, a feature that can make the corresponding physiological transcript NMD-sensitive. Here, we demonstrate that in UPF1-depleted or in cycloheximide-treated HeLa and HepG2 cells the HFE transcripts are clearly upregulated, meaning that the physiological HFE mRNA is in fact an NMD-target. This role of NMD in controlling the HFE expression levels was further confirmed in HeLa cells transiently expressing the HFE human gene. Besides, we show, by 3′-RACE analysis in several human tissues that HFE mRNA expression results from alternative cleavage and polyadenylation at four different sites – two were previously described and two are novel polyadenylation sites: one located at exon six, which confers NMD-resistance to the corresponding transcripts, and another located at exon seven. In addition, we show that the amount of HFE mRNA isoforms resulting from cleavage and polyadenylation at exon seven, although present in both cell lines, is higher in HepG2 cells. These results reveal that NMD and alternative polyadenylation may act coordinately to control HFE mRNA levels, possibly varying its

  4. Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.

    Directory of Open Access Journals (Sweden)

    Cécile Méjécase

    Full Text Available GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321* in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321* is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.

  5. Transcribing nonsense words: The effect of numbers of voices and repetitions.

    Science.gov (United States)

    Knight, Rachael-Anne

    2010-06-01

    Transcription skills are crucially important to all phoneticians, and particularly for speech and language therapists who may use transcriptions to make decisions about diagnosis and intervention. Whilst interest in factors affecting transcription accuracy is increasing, there are still a number of issues that are yet to be investigated. The present paper considers how the number of voices and the number of repetitions affects the transcription of nonsense words. Thirty-two students in their second year of study for a BSc in Speech and Language Therapy were participants in an experiment. They heard two nonsense words presented 10 times in either one or two voices. Results show that the number of voices did not affect accuracy, but that accuracy increased between six and ten repetitions. The reasons behind these findings, and implications for teaching and learning, and further research are discussed.

  6. Breve fenomenologia del lettore ai confini del nonsense (o Il lettore provocato

    Directory of Open Access Journals (Sweden)

    Laura Lucia Rossi

    2012-12-01

    Full Text Available In questo articolo esaminiamo alcuni generi letterari che sono stati spesso accostati al nonsense letterario. In particolare prendiamo in considerazione il ruolo del lettore all’interno di questi testi e ne proponiamo una sorta di fenomenologia. Invitiamo, infine, a riflettere su come considerare la dimensione del lettore all’interno di un genere letterario possa condurre a risultati rilevanti circa la definizione del genere stesso.

  7. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

  8. Nonsense mutations in the human β-globin gene affect mRNA metabolism

    International Nuclear Information System (INIS)

    Baserga, S.J.; Benz, E.J. Jr.

    1988-01-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human α- and β-globin genes. Studies on mRNA isolated from patients with β 0 -thalassemia have shown that for both the β-17 and the β-39 mutations less than normal levels of β-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human β-globin mRNA). In vitro studies using the cloned β-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human β-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation

  9. Sense and nonsense in metabolic control of reproduction.

    Science.gov (United States)

    Schneider, Jill E; Klingerman, Candice M; Abdulhay, Amir

    2012-01-01

    An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

  10. Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

    2003-02-01

    Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

  11. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic......, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest...

  12. Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell lung cancer but retains sensitivity to afatinib.

    Science.gov (United States)

    Liu, Yutao; Li, Yan; Ou, Qiuxiang; Wu, Xue; Wang, Xiaonan; Shao, Yang W; Ying, Jianming

    2018-04-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are promising targeted therapies for EGFR-mutated non-small-cell lung cancer (NSCLC) patients. However, acquired resistance inevitably develops. Comprehensive and dynamic companion genomic diagnosis can gain insights into underlying resistance mechanisms, thereby help oncologists and patients to make informed decision on the potential benefit of the treatment. A 67-year-old male who was initially diagnosed of EGFR L858R-mediated NSCLC received multiple lines of chemotherapy and EGFR TKI therapies after surgery. The EGFR mutational status of individual metastatic lesion was determined by genetic testing of the tumor tissue biopsies using next generation sequencing (NGS) throughout the patient's clinical course. An acquired potentially drug-resistant EGFR mutation was functionally validated in vitro and its sensitivity to different EGFR TKIs was assessed simultaneously. We have identified distinct resistance mechanisms to EGFR blockade in different metastatic lung lesions. Acquired EGFR T790M was first detected that leads to the resistance to the gefitinib treatment. Consequently, osimertinib was administrated and the response lasted until disease progressed. We identified a newly acquired EGFR L718V mutation in one lesion in conjunction with L858R, but not T790M, which showed stable disease on the following erlotinib treatment, while EGFR C797S together with L858R/T790M was detected in the other lesion that continuously progressed. In vitro functional studies demonstrated that EGFR-L858R/L718V confers resistance to osimertinib, but retains sensitivity to the second generation TKI afatinib. We reported that distinct resistance mechanisms could arise in different metastases within the same patient in response to EGFR blockade. We also demonstrated in vitro that EGFR L718V mutation mediates resistance to osimertinib, but retains sensitivity to afatinib. We evidenced that dynamic companion genomic

  13. A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.

    Science.gov (United States)

    Nicolas, Gaël; Jacquin, Agnès; Thauvin-Robinet, Christel; Rovelet-Lecrux, Anne; Rouaud, Olivier; Pottier, Cyril; Aubriot-Lorton, Marie-Hélène; Rousseau, Stéphane; Wallon, David; Duvillard, Christian; Béjot, Yannick; Frébourg, Thierry; Giroud, Maurice; Campion, Dominique; Hannequin, Didier

    2014-10-01

    Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.

  14. A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family.

    Science.gov (United States)

    Yao, Ke; Jin, Chongfei; Zhu, Ning; Wang, Wei; Wu, Renyi; Jiang, Jin; Shentu, Xingchao

    2008-07-09

    To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant gammaC-crystallin were generated and analyzed by SWISS-MODEL. Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated gammaC-crystallin. A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.

  15. Translational read-through of a nonsense mutation causing Bartter syndrome.

    Science.gov (United States)

    Cho, Hee Yeon; Lee, Beom Hee; Cheong, Hae Il

    2013-06-01

    Bartter syndrome (BS) is classified into 5 genotypes according to underlying mutant genes and BS III is caused by loss-of-function mutations in the CLCNKB gene encoding for basolateral ClC-Kb. BS III is the most common genotype in Korean patients with BS and W610X is the most common CLCNKB mutation in Korean BS III. In this study, we tested the hypothesis that the CLCNKB W610X mutation can be rescued in vitro using aminoglycoside antibiotics, which are known to induce translational read-through of a nonsense mutation. The CLCNKB cDNA was cloned into a eukaryotic expression vector and the W610X nonsense mutation was generated by site-directed mutagenesis. Cultured polarized MDCK cells were transfected with the vectors, and the read-through was induced using an aminoglycoside derivative, G418. Cellular expression of the target protein was monitored via immunohistochemistry. While cells transfected with the mutant CLCNKB failed to express ClC-Kb, G418 treatment of the cells induced the full-length protein expression, which was localized to the basolateral plasma membranes. It is demonstrated that the W610X mutation in CLCNKB can be a good candidate for trial of translational read-through induction as a therapeutic modality.

  16. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation

    DEFF Research Database (Denmark)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian Gryesten

    2011-01-01

    Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation......Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a danish five-generation family with a novel FAM83H nonsense mutation...

  17. Effects of Temporal Sequencing and Auditory Discrimination on Children's Memory Patterns for Tones, Numbers, and Nonsense Words

    Science.gov (United States)

    Gromko, Joyce Eastlund; Hansen, Dee; Tortora, Anne Halloran; Higgins, Daniel; Boccia, Eric

    2009-01-01

    The purpose of this study was to determine whether children's recall of tones, numbers, and words was supported by a common temporal sequencing mechanism; whether children's patterns of memory for tones, numbers, and nonsense words were the same despite differences in symbol systems; and whether children's recall of tones, numbers, and nonsense…

  18. Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency.

    Science.gov (United States)

    Branchini, A; Ferrarese, M; Lombardi, S; Mari, R; Bernardi, F; Pinotti, M

    2016-10-01

    Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild

  19. Nonsense-Mediated RNA Decay Influences Human Embryonic Stem Cell Fate

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    Chih-Hong Lou

    2016-06-01

    Full Text Available Nonsense-mediated RNA decay (NMD is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

  20. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

    Science.gov (United States)

    Witting, N; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Perception of emotional nonsense sentences in China, Egypt, Estonia, Finland, Russia, Sweden, and the USA.

    Science.gov (United States)

    Waaramaa, Teija

    2015-10-01

    The present study focused on the identification of emotions in cross-cultural conditions on different continents and among subjects with divergent language backgrounds. The aim was to investigate whether the perception of the basic emotions from nonsense vocal samples was universal, dependent on voice quality, musicality, and/or gender. Listening tests for 350 participants were conducted on location in a variety of cultures: China, Egypt, Estonia, Finland, Russia, Sweden, and the USA. The results suggested that the voice quality parameters played a role in the identification of emotions without the linguistic content. Cultural background may affect the interpretation of the emotions more than the presumed universality. Musical interest tended to facilitate emotion identification. No gender differences were found.

  2. O Maravilhoso País do Orkut: sobre jogos, racionalidade , nonsense e frivolidades

    Directory of Open Access Journals (Sweden)

    Angela Prysthon

    2008-12-01

    Full Text Available Departing from the concept of Homo Ludens by Johan Huizinga, from the connections between Aesthetics and everyday experience, from some Habermasian notions of rationality and from the nonsense as deployed by Deleuze, this essay intends to relate the fascination for banality and the consolidation of an aesthetics of frivolity (both very present in the Orkut with the ideas of rationality and the ludic in contemporary culture. If the Orkut appeared as a platform of social networking, it is indubitable the proliferation of games and “inutilities” in the system (especially in its Brazilian branch. In this sense, playfulness, laughter, the ephemeral, frivolities, all of this form the kernel of our analysis of Orkut.

  3. Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim Lütken; Waage, Johannes Eichler; Tian, Geng

    2012-01-01

    ABSTRACT: BACKGROUND: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation...... of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2. RESULTS: We developed...... importance, the latter events are associated with high intronic conservation. CONCLUSIONS: Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel...

  4. Association of a Novel Nonsense Mutation in KIAA1279 with Goldberg-Shprintzen Syndrome.

    Science.gov (United States)

    Salehpour, Shadab; Hashemi-Gorji, Feyzollah; Soltani, Ziba; Ghafouri-Fard, Soudeh; Miryounesi, Mohammad

    2017-01-01

    Goldberg-Shprintzen syndrome (OMIM 609460) (GOSHS) is an autosomal recessive multiple congenital anomaly syndrome distinguished by intellectual disability, microcephaly, and dysmorphic facial characteristics. Most affected individuals also have Hirschsprung disease and/or gyral abnormalities of the brain. This syndrome has been associated with KIAA1279 gene mutations at 10q22.1. Here we report a 16 yr old male patient referred to Center for Comprehensive Genetic Services, Tehran, Iran in 2015 with cardinal features of GOSHS in addition to refractory seizures. Whole exome sequencing in the patient revealed a novel nonsense (stop gain) homozygous mutation in KIAA1279 gene (KIAA1279: NM_015634:exon6:c.C976T:p.Q326X). Considering the wide range of phenotypic variations in GOSHS, relying on phenotypic characteristics for discrimination of GOSH from similar syndromes may lead to misdiagnosis. Consequently, molecular diagnostic tools would help in accurate diagnosis of such overlapping phenotypes.

  5. Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

    International Nuclear Information System (INIS)

    Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

    2015-01-01

    Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

  6. Nonsense-mediated mRNA decay and loss-of-function of the protein underlie the X-linked epilepsy associated with the W356× mutation in synapsin I.

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    Maila Giannandrea

    Full Text Available Synapsins are a family of neuronal phosphoproteins associated with the cytosolic surface of synaptic vesicles. Experimental evidence suggests a role for synapsins in synaptic vesicle clustering and recycling at the presynaptic terminal, as well as in neuronal development and synaptogenesis. Synapsin knock-out (Syn1(-/- mice display an epileptic phenotype and mutations in the SYN1 gene have been identified in individuals affected by epilepsy and/or autism spectrum disorder. We investigated the impact of the c.1067G>A nonsense transition, the first mutation described in a family affected by X-linked syndromic epilepsy, on the expression and functional properties of the synapsin I protein. We found that the presence of a premature termination codon in the human SYN1 transcript renders it susceptible to nonsense-mediated mRNA decay (NMD. Given that the NMD efficiency is highly variable among individuals and cell types, we investigated also the effects of expression of the mutant protein and found that it is expressed at lower levels compared to wild-type synapsin I, forms perinuclear aggregates and is unable to reach presynaptic terminals in mature hippocampal neurons grown in culture. Taken together, these data indicate that in patients carrying the W356× mutation the function of synapsin I is markedly impaired, due to both the strongly decreased translation and the altered function of the NMD-escaped protein, and support the value of Syn1(-/- mice as an experimental model mimicking the human pathology.

  7. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

    Science.gov (United States)

    2012-01-01

    Background Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis. PMID:22938382

  8. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3.

    Science.gov (United States)

    Eisenberger, Tobias; Slim, Rima; Mansour, Ahmad; Nauck, Markus; Nürnberg, Gudrun; Nürnberg, Peter; Decker, Christian; Dafinger, Claudia; Ebermann, Inga; Bergmann, Carsten; Bolz, Hanno Jörn

    2012-09-02

    Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.

  9. Congenital Mirror Movements Due to RAD51: Cosegregation with a Nonsense Mutation in a Norwegian Pedigree and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Oriane Trouillard

    2016-11-01

    Full Text Available Background: Autosomal dominant congenital mirror movements (CMM is a neurodevelopmental disorder characterized by early onset involuntary movements of one side of the body that mirror intentional movements on the contralateral side; these persist throughout life in the absence of other neurological symptoms. The main culprit genes responsible for this condition are RAD51 and DCC. This condition has only been reported in a few families, and the molecular mechanisms linking RAD51 mutations and mirror movements (MM are poorly understood. Methods: We collected demographic, clinical, and genetic data of a new family with CMM due to a truncating mutation of RAD51. We reviewed the literature to identify all reported patients with CMM due to RAD51 mutations. Results: We identified a heterozygous nonsense mutation c.760C>T (p.Arg254∗ in eight subjects: four with obvious and disabling MM, and four with a mild phenotype. Including our new family, we identified 32 patients from 6 families with CMM linked to RAD51 variants. Discussion: Our findings further support the involvement of RAD51 in CMM pathogenesis. Possible molecular mechanisms involved in CMM pathogenesis are discussed.

  10. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3

    Directory of Open Access Journals (Sweden)

    Eisenberger Tobias

    2012-09-01

    Full Text Available Abstract Background Usher syndrome (USH is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP. We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3. Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract. After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.

  11. Novel nonsense mutation in the katA gene of a catalase-negative Staphylococcus aureus strain.

    Science.gov (United States)

    Lagos, Jaime; Alarcón, Pedro; Benadof, Dona; Ulloa, Soledad; Fasce, Rodrigo; Tognarelli, Javier; Aguayo, Carolina; Araya, Pamela; Parra, Bárbara; Olivares, Berta; Hormazábal, Juan Carlos; Fernández, Jorge

    2016-01-01

    We report the first description of a rare catalase-negative strain of Staphylococcus aureus in Chile. This new variant was isolated from blood and synovial tissue samples of a pediatric patient. Sequencing analysis revealed that this catalase-negative strain is related to ST10 strain, which has earlier been described in relation to S. aureus carriers. Interestingly, sequence analysis of the catalase gene katA revealed presence of a novel nonsense mutation that causes premature translational truncation of the C-terminus of the enzyme leading to a loss of 222 amino acids. Our study suggests that loss of catalase activity in this rare catalase-negative Chilean strain is due to this novel nonsense mutation in the katA gene, which truncates the enzyme to just 283 amino acids. Copyright © 2015 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.

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    Richard S Finkel

    Full Text Available Approximately 13% of boys with Duchenne muscular dystrophy (DMD have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124 enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins.This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6 received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20 was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12 was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint.Twenty three of 38 (61% subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated.Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD.ClinicalTrials.gov NCT00264888.

  13. A Nonsense Variant in the ACADVL Gene in German Hunting Terriers with Exercise Induced Metabolic Myopathy

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    Vincent Lepori

    2018-05-01

    Full Text Available Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1 peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD. Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*. The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM, and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring.

  14. On the problem of nonsense correlations in allergological tests after routine extraction.

    Science.gov (United States)

    Rijckaert, G

    1981-01-01

    The influence of extraction procedures and culturing methods of material used for the preparation of allergenic extracts on correlation patterns found in allergological testing (skin test and RAST) was investigated. In our laboratory a short extraction procedure performed at O degrees C was used for Aspergillus repens. A. penicilloides, Wallemia sebi, their rearing media and non-inoculated medium. For the commercially available extracts from house dust, house-dust mite, pollen of Dactylus glomerata and A. penicilloides a longer procedure (several days) performed at room temperature was used. Statistical analysis showed a separation of all test results into two clusters, each cluster being composed of correlations between extracts from only one the manufacturers did not show any correlation. The correlations found between the short time incubated extracts of the xerophilic fungi and their rearing media could be explained by genetical and biochemical relationships between these fungi depending on ecological conditions. However, while the correlation found between house dust and house-dust mite is understandable, correlations found between long time incubated extracts from house-dust mite and D. glomerata or A. penicilloides may be nonsense correlations, that do not adequately describe the in vivo situation. The similarity of these extracts is presumably artificially created during extraction.

  15. A Nonsense Variant in the ACADVL Gene in German Hunting Terriers with Exercise Induced Metabolic Myopathy.

    Science.gov (United States)

    Lepori, Vincent; Mühlhause, Franziska; Sewell, Adrian C; Jagannathan, Vidhya; Janzen, Nils; Rosati, Marco; Alves de Sousa, Filipe Miguel Maximiano; Tschopp, Aurélie; Schüpbach, Gertraud; Matiasek, Kaspar; Tipold, Andrea; Leeb, Tosso; Kornberg, Marion

    2018-05-04

    Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM), and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring. Copyright © 2018 Lepori et al.

  16. Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene

    International Nuclear Information System (INIS)

    Romeo, G.; Hassan, H.J.; Staempfli, S.

    1987-01-01

    The structure of the gene for protein C, an anticoagulant serine protease, was analyzed in 29 unrelated patients with hereditary thrombophilia and protein C deficiency. Gene deletion(s) or gross rearrangement(s) was not demonstrable by Southern blot hybridization to cDNA probes. However, two unrelated patients showed a variant restriction pattern after Pvu II or BamHi digestion, due to mutations in the last exon: analysis of their pedigrees, including three or seven heterozygotes, respectively, with ∼50% reduction of both enzymatic and antigen level, showed the abnormal restriction pattern in all heterozygous individuals, but not in normal relatives. Cloning of protein C gene and sequencing of the last exon allowed the authors to identify a nonsense and a missense mutation, respectively. In the first case, codon 306 (CGA, arginine) is mutated to an inframe stop codon, thus generating a new Pvu II recognition site. In the second case, a missense mutation in the BamHI palindrome (GGATCC → GCATCC) leads to substitution of a key amino acid (a tryptophan to cysteine substitution at position 402), invariantly conserved in eukaryotic serine proteases. These point mutations may explain the protein C-deficiency phenotype of heterozygotes in the two pedigrees

  17. Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism.

    Science.gov (United States)

    Amselem, S; Sobrier, M L; Duquesnoy, P; Rappaport, R; Postel-Vinay, M C; Gourmelen, M; Dallapiccola, B; Goossens, M

    1991-01-01

    In addition to its classical effects on growth, growth hormone (GH) has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues. Purification of a rabbit liver protein via its ability to bind GH has allowed the isolation of a cDNA encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors. We have previously shown that this putative growth hormone receptor gene is genetically linked to Laron dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH. Nevertheless, the inability to express the corresponding full-length coding sequence and the lack of a test for growth-promoting function have hampered a direct confirmation of its role in growth. We have now identified three nonsense mutations within this growth hormone receptor gene, lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule, thereby deleting a large portion of both the GH binding domain and the full transmembrane and intracellular domains. Three independent patients with Laron dwarfism born of consanguineous parents were homozygous for these defects. Two defects were identical and consisted of a CG to TG transition. Not only do these results confirm the growth-promoting activity of this receptor but they also suggest that CpG doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism. Images PMID:1999489

  18. NMD Classifier: A reliable and systematic classification tool for nonsense-mediated decay events.

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    Min-Kung Hsu

    Full Text Available Nonsense-mediated decay (NMD degrades mRNAs that include premature termination codons to avoid the translation and accumulation of truncated proteins. This mechanism has been found to participate in gene regulation and a wide spectrum of biological processes. However, the evolutionary and regulatory origins of NMD-targeted transcripts (NMDTs have been less studied, partly because of the complexity in analyzing NMD events. Here we report NMD Classifier, a tool for systematic classification of NMD events for either annotated or de novo assembled transcripts. This tool is based on the assumption of minimal evolution/regulation-an event that leads to the least change is the most likely to occur. Our simulation results indicate that NMD Classifier can correctly identify an average of 99.3% of the NMD-causing transcript structural changes, particularly exon inclusions/exclusions and exon boundary alterations. Researchers can apply NMD Classifier to evolutionary and regulatory studies by comparing NMD events of different biological conditions or in different organisms.

  19. Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense Mediated mRNA Decay.

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    Grigorios Fanourgakis

    2016-05-01

    Full Text Available Chromatoid bodies (CBs are spermiogenesis-specific organelles of largely unknown function. CBs harbor various RNA species, RNA-associated proteins and proteins of the tudor domain family like TDRD6, which is required for a proper CB architecture. Proteome analysis of purified CBs revealed components of the nonsense-mediated mRNA decay (NMD machinery including UPF1. TDRD6 is essential for UPF1 localization to CBs, for UPF1-UPF2 and UPF1-MVH interactions. Upon removal of TDRD6, the association of several mRNAs with UPF1 and UPF2 is disturbed, and the long 3' UTR-stimulated but not the downstream exon-exon junction triggered pathway of NMD is impaired. Reduced association of the long 3' UTR mRNAs with UPF1 and UPF2 correlates with increased stability and enhanced translational activity. Thus, we identified TDRD6 within CBs as required for mRNA degradation, specifically the extended 3' UTR-triggered NMD pathway, and provide evidence for the requirement of NMD in spermiogenesis. This function depends on TDRD6-promoted assembly of mRNA and decay enzymes in CBs.

  20. Molecular analysis of congenital goitres with hypothyroidism caused by defective thyroglobulin synthesis. Identification of a novel c.7006C>T [p.R2317X] mutation and expression of minigenes containing nonsense mutations in exon 7.

    Science.gov (United States)

    Machiavelli, Gloria A; Caputo, Mariela; Rivolta, Carina M; Olcese, María C; Gruñeiro-Papendieck, Laura; Chiesa, Ana; González-Sarmiento, Rogelio; Targovnik, Héctor M

    2010-01-01

    Thyroglobulin (TG) deficiency is an autosomal-recessive disorder that results in thyroid dyshormonogenesis. A number of distinct mutations have been identified as causing human hypothyroid goitre. The purpose of this study was to identify and characterize new mutations in the TG gene in an attempt to increase the understanding of the genetic mechanism responsible for this disorder. A total of six patients from four nonconsanguineous families with marked impairment of TG synthesis were studied. Single-strand conformation polymorphism (SSCP) analysis, sequencing of DNA, genotyping, expression of chimeric minigenes and bioinformatic analysis were performed. Four different inactivating TG mutations were identified: one novel mutation (c.7006C>T [p.R2317X]) and three previously reported (c.886C>T [p.R277X], c.6701C>A [p.A2215D] and c.6725G>A [p.R2223H]). Consequently, one patient carried a compound heterozygous for p.R2223H/p.R2317X mutations; two brothers showed a homozygous p.A2215D substitution and the remaining three patients, from two families with typical phenotype, had a single p.R277X mutated allele. We also showed functional evidences that premature stop codons inserted at different positions in exon 7, which disrupt exonic splicing enhancer (ESE) sequences, do not interfere with exon definition and processing. In this study, we have identified a novel nonsense mutation p.R2317X in the acetylcholinesterase homology domain of TG. We have also observed that nonsense mutations do not interfere with the pre-mRNA splicing of exon 7. The results are in accordance with previous observations confirming the genetic heterogeneity of TG defects.

  1. Targeted next-generation sequencing identifies a novel nonsense mutation in SPTB for hereditary spherocytosis: A case report of a Korean family.

    Science.gov (United States)

    Shin, Soyoung; Jang, Woori; Kim, Myungshin; Kim, Yonggoo; Park, Suk Young; Park, Joonhong; Yang, Young Jun

    2018-01-01

    Hereditary spherocytosis (HS) is an inherited disorder characterized by the presence of spherical-shaped red blood cells (RBCs) on the peripheral blood (PB) smear. To date, a number of mutations in 5 genes have been identified and the mutations in SPTB gene account for about 20% patients. A 65-year-old female had been diagnosed as hemolytic anemia 30 years ago, based on a history of persistent anemia and hyperbilirubinemia for several years. She received RBC transfusion several times and a cholecystectomy roughly 20 years ago before. Round, densely staining spherical-shaped erythrocytes (spherocytes) were frequently found on the PB smear. Numerous spherocytes were frequently found in the PB smears of symptomatic family members, her 3rd son and his 2 grandchildren. One heterozygous mutation of SPTB was identified by targeted next-generation sequencing (NGS). The nonsense mutation, c.1956G>A (p.Trp652*), in exon 13 was confirmed by Sanger sequencing and thus the proband was diagnosed with HS. The proband underwent a splenectomy due to transfusion-refractory anemia and splenomegaly. After the splenectomy, her hemoglobin level improved to normal range (14.1 g/dL) and her bilirubin levels decreased dramatically (total bilirubin 1.9 mg/dL; direct bilirubin 0.6 mg/dL). We suggest that NGS of causative genes could be a useful diagnostic tool for the genetically heterogeneous RBC membrane disorders, especially in cases with a mild or atypical clinical manifestation. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  2. Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mohan Narayanan

    2015-09-01

    Full Text Available Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy, or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome.   In this case report, we present the clinical features of siblings (brother and sister with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93* and c.397C>T (p.Arg133*, in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus.   Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus.

  3. Heritability in the efficiency of nonsense-mediated mRNA decay in humans.

    LENUS (Irish Health Repository)

    Seoighe, Cathal

    2010-01-01

    BACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. PRINCIPAL FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3.

  4. Heritability in the efficiency of nonsense-mediated mRNA decay in humans

    KAUST Repository

    Seoighe, Cathal

    2010-07-21

    Background: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. Principal Findings: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. Conclusions: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3. © 2010 Seoighe, Gehring.

  5. Functions of the nonsense-mediated mRNA decay pathway in Drosophila development.

    Directory of Open Access Journals (Sweden)

    Mark M Metzstein

    2006-12-01

    Full Text Available Nonsense-mediated mRNA decay (NMD is a cellular surveillance mechanism that degrades transcripts containing premature translation termination codons, and it also influences expression of certain wild-type transcripts. Although the biochemical mechanisms of NMD have been studied intensively, its developmental functions and importance are less clear. Here, we describe the isolation and characterization of Drosophila "photoshop" mutations, which increase expression of green fluorescent protein and other transgenes. Mapping and molecular analyses show that photoshop mutations are loss-of-function mutations in the Drosophila homologs of NMD genes Upf1, Upf2, and Smg1. We find that Upf1 and Upf2 are broadly active during development, and they are required for NMD as well as for proper expression of dozens of wild-type genes during development and for larval viability. Genetic mosaic analysis shows that Upf1 and Upf2 are required for growth and/or survival of imaginal cell clones, but this defect can be overcome if surrounding wild-type cells are eliminated. By contrast, we find that the PI3K-related kinase Smg1 potentiates but is not required for NMD or for viability, implying that the Upf1 phosphorylation cycle that is required for mammalian and Caenorhabditis elegans NMD has a more limited role during Drosophila development. Finally, we show that the SV40 3' UTR, present in many Drosophila transgenes, targets the transgenes for regulation by the NMD pathway. The results establish that the Drosophila NMD pathway is broadly active and essential for development, and one critical function of the pathway is to endow proliferating imaginal cells with a competitive growth advantage that prevents them from being overtaken by other proliferating cells.

  6. Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

    Science.gov (United States)

    Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Valenti, Vincenza; Ingrassia, Valeria; Giammanco, Antonina; Panno, Maria D; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

    2015-12-01

    Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype occurring later in life in the proband and her brother and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance. © 2015 American Heart Association, Inc.

  7. Identification of a nonsense mutation in CWC15 associated with decreased reproductive efficiency in Jersey cattle.

    Directory of Open Access Journals (Sweden)

    Tad S Sonstegard

    Full Text Available With the recent advent of genomic tools for cattle, several recessive conditions affecting fertility have been identified and selected against, such as deficiency of uridine monophosphate synthase, complex vertebral malformation, and brachyspina. The current report refines the location of a recessive haplotype affecting fertility in Jersey cattle using crossover haplotypes, discovers the causative mutation using whole genome sequencing, and examines the gene's role in embryo loss. In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian sampling of 5,288 Jersey cattle was conducted for high-frequency haplotypes that have a deficit of homozygotes at the population level. This search led to the discovery of a putative recessive lethal in Jersey cattle on Bos taurus autosome 15. The haplotype, denoted JH1, was associated with reduced fertility, and further investigation identified one highly-influential Jersey bull as the putative source ancestor. By combining SNP analysis of whole-genome sequences aligned to the JH1 interval and subsequent SNP validation a nonsense mutation in CWC15 was identified as the likely causative mutation underlying the fertility phenotype. No homozygous recessive individuals were found in 749 genotyped animals, whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. This newly identified lethal has been responsible for a substantial number of spontaneous abortions in Jersey dairy cattle throughout the past half-century. With the mutation identified, selection against the deleterious allele in breeding schemes will aid in reducing the incidence of this defect in the population. These results also show that carrier status can be imputed with high accuracy. Whole-genome resequencing proved to be a powerful strategy to rapidly identify a previously mapped deleterious mutation in a known carrier of a recessive lethal allele.

  8. Consonant and Vowel Identification in Cochlear Implant Users Measured by Nonsense Words: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Rødvik, Arne Kirkhorn; von Koss Torkildsen, Janne; Wie, Ona Bø; Storaker, Marit Aarvaag; Silvola, Juha Tapio

    2018-04-17

    The purpose of this systematic review and meta-analysis was to establish a baseline of the vowel and consonant identification scores in prelingually and postlingually deaf users of multichannel cochlear implants (CIs) tested with consonant-vowel-consonant and vowel-consonant-vowel nonsense syllables. Six electronic databases were searched for peer-reviewed articles reporting consonant and vowel identification scores in CI users measured by nonsense words. Relevant studies were independently assessed and screened by 2 reviewers. Consonant and vowel identification scores were presented in forest plots and compared between studies in a meta-analysis. Forty-seven articles with 50 studies, including 647 participants, thereof 581 postlingually deaf and 66 prelingually deaf, met the inclusion criteria of this study. The mean performance on vowel identification tasks for the postlingually deaf CI users was 76.8% (N = 5), which was higher than the mean performance for the prelingually deaf CI users (67.7%; N = 1). The mean performance on consonant identification tasks for the postlingually deaf CI users was higher (58.4%; N = 44) than for the prelingually deaf CI users (46.7%; N = 6). The most common consonant confusions were found between those with same manner of articulation (/k/ as /t/, /m/ as /n/, and /p/ as /t/). The mean performance on consonant identification tasks for the prelingually and postlingually deaf CI users was found. There were no statistically significant differences between the scores for prelingually and postlingually deaf CI users. The consonants that were incorrectly identified were typically confused with other consonants with the same acoustic properties, namely, voicing, duration, nasality, and silent gaps. A univariate metaregression model, although not statistically significant, indicated that duration of implant use in postlingually deaf adults predict a substantial portion of their consonant identification ability. As there is no ceiling

  9. Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina.

    Science.gov (United States)

    Goldmann, Tobias; Rebibo-Sabbah, Annie; Overlack, Nora; Nudelman, Igor; Belakhov, Valery; Baasov, Timor; Ben-Yosef, Tamar; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin

    2010-12-01

    The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. USH is clinically and genetically heterogeneous, assigned to three clinical types. The most severe type is USH1, characterized by profound inner ear defects and retinitis pigmentosa. Thus far, no effective treatment for the ophthalmic component of USH exists. The p.R31X nonsense mutation in USH1C leads to a disease causing premature termination of gene translation. Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option. Read-through of p.R31X by three commercial, clinically applied aminoglycosides and the synthetic derivative NB30 was validated in vitro, in cell culture, and in retinal explants. Restoration of harmonin functions was monitored in GST pull-downs (scaffold function) and by F-actin bundling analysis in HEK293T cells. Biocompatibility of aminoglycosides was determined in retinal explants by TUNEL assays. In vitro translation and analyses of transfected HEK293T cells revealed a dose-dependent read-through by all aminoglycosides. In addition, gentamicin, paromomycin, and NB30 induced read-through of p.R31X in mouse retinal explants. The read-through of p.R31X restored harmonin protein function. In contrast to all commercial aminoglycosides NB30 showed good biocompatibility. Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation. However, the observed read-through efficiency, along with its significantly reduced toxicity and good biocompatibility, indicate that the novel derivate NB30 represents a better choice than commercial aminoglycosides in a read-through therapy of USH1C and other ocular diseases.

  10. The application of nonsense-mediated mRNA decay inhibition to the identification of breast cancer susceptibility genes

    International Nuclear Information System (INIS)

    Johnson, Julie K; Waddell, Nic; Chenevix-Trench, Georgia

    2012-01-01

    Identification of novel, highly penetrant, breast cancer susceptibility genes will require the application of additional strategies beyond that of traditional linkage and candidate gene approaches. Approximately one-third of inherited genetic diseases, including breast cancer susceptibility, are caused by frameshift or nonsense mutations that truncate the protein product [1]. Transcripts harbouring premature termination codons are selectively and rapidly degraded by the nonsense-mediated mRNA decay (NMD) pathway. Blocking the NMD pathway in any given cell will stabilise these mutant transcripts, which can then be detected using gene expression microarrays. This technique, known as gene identification by nonsense-mediated mRNA decay inhibition (GINI), has proved successful in identifying sporadic nonsense mutations involved in many different cancer types. However, the approach has not yet been applied to identify germline mutations involved in breast cancer. We therefore attempted to use GINI on lymphoblastoid cell lines (LCLs) from multiple-case, non- BRCA1/2 breast cancer families in order to identify additional high-risk breast cancer susceptibility genes. We applied GINI to a total of 24 LCLs, established from breast-cancer affected and unaffected women from three multiple-case non-BRCA1/2 breast cancer families. We then used Illumina gene expression microarrays to identify transcripts stabilised by the NMD inhibition. The expression profiling identified a total of eight candidate genes from these three families. One gene, PPARGC1A, was a candidate in two separate families. We performed semi-quantitative real-time reverse transcriptase PCR of all candidate genes but only PPARGC1A showed successful validation by being stabilised in individuals with breast cancer but not in many unaffected members of the same family. Sanger sequencing of all coding and splice site regions of PPARGC1A did not reveal any protein truncating mutations. Haplotype analysis using short

  11. CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

    Science.gov (United States)

    Busi, Florent; Cresteil, Thierry

    2005-09-01

    The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2 cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5 mRNA decay. Splice variants containing exon 3B were more unstable than wild-type (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of exon 3B-containing splice variants, suggesting the participation of nonsense-mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1 small interfering RNA was used to impair the NMD mechanism, the decay of the splice variant was reduced, confirming the involvement of NMD in the degradation of CYP3A5 splice variants. Induction could represent a source of variability for CYP3A5 expression and could modify the proportion of splice variants. The extent of CYP3A5 induction was investigated after exposure to barbiturates or steroids: CYP3A4 was markedly induced in a pediatric population compared with untreated neonates. However, no effect could be detected in either the total CYP3A5 RNA, the proportion of splice variant RNA, or the protein level. Therefore, in these carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in carriers of CYP3A5*3/*3.

  12. A Novel Nonsense Mutation in the DMP1 Gene Identified by a Genome-Wide Association Study Is Responsible for Inherited Rickets in Corriedale Sheep

    Science.gov (United States)

    Blair, Hugh T.; Thompson, Keith G.; Rothschild, Max F.; Garrick, Dorian J.

    2011-01-01

    Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP) loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1) was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were “T T” genotypes; the 3 carriers were “C T”; 24 phenotypically normal related sheep were either “C T” or “C C”; and 46 unrelated normal control sheep from other breeds were all “C C”. The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis. PMID:21747952

  13. Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.

    Science.gov (United States)

    Huizing, Marjan; Scher, Charles D; Strovel, Erin; Fitzpatrick, Diana L; Hartnell, Lisa M; Anikster, Yair; Gahl, William A

    2002-02-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease consisting of oculocutaneous albinism and a storage pool deficiency resulting from absent platelet dense bodies. The disorder is genetically heterogeneous. The majority of patients, including members of a large genetic isolate in northwest Puerto Rico, have mutations in HPS1. Another gene, ADTB3A, was shown to cause HPS-2 in two brothers having compound heterozygous mutations that allowed for residual production of the gene product, the beta3A subunit of adaptor complex-3 (AP-3). This heterotetrameric complex serves as a coat protein-mediating formation of intracellular vesicles, e.g. the melanosome and platelet dense body, from membranes of the trans-Golgi network. We determined the genomic organization of the human ADTB3A gene, with intron/exon boundaries, and describe a third patient with beta3A deficiency. This 5-y-old boy has two nonsense mutations, C1578T (R-->X) and G2028T (E-->X), which produce no ADTB3A mRNA and no beta3A protein. The associated mu3 subunit of AP-3 is also entirely absent. In fibroblasts, the cell biologic concomitant of this deficiency is robust and aberrant trafficking through the plasma membrane of LAMP-3, an integral lysosomal membrane protein normally carried directly to the lysosome. The clinical concomitant is a severe, G-CSF-responsive neutropenia in addition to oculocutaneous albinism and platelet storage pool deficiency. Our findings expand the molecular, cellular, and clinical spectrum of HPS-2 and call for an increased index of suspicion for this diagnosis among patients with features of albinism, bleeding, and neutropenia.

  14. A novel nonsense mutation in the DMP1 gene identified by a genome-wide association study is responsible for inherited rickets in Corriedale sheep.

    Directory of Open Access Journals (Sweden)

    Xia Zhao

    Full Text Available Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1 was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were "T T" genotypes; the 3 carriers were "C T"; 24 phenotypically normal related sheep were either "C T" or "C C"; and 46 unrelated normal control sheep from other breeds were all "C C". The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective "T" allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis.

  15. New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors.

    Science.gov (United States)

    Raimondeau, Etienne; Bufton, Joshua C; Schaffitzel, Christiane

    2018-06-19

    Faulty mRNAs with a premature stop codon (PTC) are recognized and degraded by nonsense-mediated mRNA decay (NMD). Recognition of a nonsense mRNA depends on translation and on the presence of NMD-enhancing or the absence of NMD-inhibiting factors in the 3'-untranslated region. Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating PTC-containing mRNAs. Our recent discovery that UPF3B interferes with human translation termination and enhances ribosome dissociation in vitro , whereas UPF1 is inactive in these assays, suggests a re-interpretation of previous experiments and modification of prevalent NMD models. Moreover, we discuss recent work suggesting new functions of the key NMD factor UPF1 in ribosome recycling, inhibition of translation re-initiation and nascent chain ubiquitylation. These new findings suggest that the interplay of UPF proteins with the translation machinery is more intricate than previously appreciated, and that this interplay quality-controls the efficiency of termination, ribosome recycling and translation re-initiation. © 2018 The Author(s).

  16. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G

    2015-06-01

    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi’s Granuloma: The Consequences of Skin Barrier Dysfunction

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2015-09-01

    Full Text Available Non-bullous congenital ichthyosiform erythroderma (NBCIE is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C>T (p.Arg272* in ALOXE3 (NM_001165960.1 in the proband and discovered that his parents are both heterozygous carriers of the variant. The clinical manifestations of the proband’s skin were consistent with NBCIE, and detailed histopathological assessment revealed epidermal bulla formation and Majocchi’s granuloma. Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. Decreased skin barrier function, such as that caused by hereditary disorders of keratinization, can increase the risk of severe cutaneous fungal infections and the formation of Majocchi’s granuloma and associated alopecia. Patients with NBCIE should be alerted to the possible predisposition for developing dermatophytoses and warrant close clinical follow-up.

  18. Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea.

    Science.gov (United States)

    Ben Hadj Hmida, Imen; Mougou-Zerelli, Soumaya; Hadded, Anis; Dimassi, Sarra; Kammoun, Molka; Bignon-Topalovic, Joelle; Bibi, Mohamed; Saad, Ali; Bashamboo, Anu; McElreavey, Ken

    2016-07-01

    To determine the genetic cause of 46,XY primary amenorrhea in three 46,XY girls. Whole exome sequencing. University cytogenetics center. Three patients with unexplained 46,XY primary amenorrhea were included in the study. Potentially pathogenic variants were confirmed by Sanger sequencing, and familial segregation was determined where parents' DNA was available. Exome sequencing was performed in the three patients, and the data were analyzed for potentially pathogenic mutations. The functional consequences of mutations were predicted. Three novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene were identified:c.1573 C→T, p.Gln525Ter, c.1435 C→T p.Arg479Ter, and c.508 C→T, p.Gln170Ter. Inactivating mutations of the LHCGR gene may be a more common cause of 46,XY primary amenorrhea than previously considered. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

    Science.gov (United States)

    Fiorini, Francesca; Robin, Jean-Philippe; Kanaan, Joanne; Borowiak, Malgorzata; Croquette, Vincent; Le Hir, Hervé; Jalinot, Pierre; Mocquet, Vincent

    2018-01-30

    Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

  20. A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Rendtorff, Nanna D; Nielsen, Morten S

    2015-01-01

    Nonsyndromic hearing impairment (NSHI) is a highly heterogeneous condition with more than eighty known causative genes. However, in the clinical setting, a large number of NSHI families have unexplained etiology, suggesting that there are many more genes to be identified. In this study we used SNP......-based linkage analysis and follow up microsatellite markers to identify a novel locus (DFNA66) on chromosome 6q15-21 (LOD 5.1) in a large Danish family with dominantly inherited NSHI. By locus specific capture and next-generation sequencing, we identified a c.574C>T heterozygous nonsense mutation (p.R192......-genome and exome sequence data. The predicted effect of the mutation was a truncation of the last six C-terminal residues of the cytoplasmic tail of CD164, including a highly conserved canonical sorting motif (YXX phi). In whole blood from an affected individual, we found by RT-PCR both the wild...

  1. A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease

    OpenAIRE

    Liu, Deyuan; Hu, Zhengmao; Peng, Yu; Yu, Changhong; Liu, Yalan; Mo, Xiaoyun; Li, Xiaoping; Lu, Lina; Xu, Xiaojuan; Su, Wei; Pan, Qian; Xia, Kun

    2010-01-01

    Purpose Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, ...

  2. A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome.

    Science.gov (United States)

    Noorian, Shahab; Savad, Shahram; Mohammadi, Davood Shah

    2016-05-01

    Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder, which is mostly caused by mutations in the WFS1 gene. The WFS1 gene product, which is called wolframin, is thought to regulate the function of endoplasmic reticulum. The endoplasmic reticulum has a critical role in protein folding and material transportation within the cell or to the surface of the cell. Identification of new mutations in WFS1 gene will unravel the molecular pathology of WS. The aim of this case report study is to describe a novel mutation in exon 4 of the WFS1 gene (c.330C>A) in a 9-year-old boy with WS.

  3. The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis.

    Science.gov (United States)

    Georgiou, Theodoros; Christopoulos, George; Anastasiadou, Violetta; Hadjiloizou, Stavros; Cregeen, David; Jackson, Marie; Mavrikiou, Gavriella; Kleanthous, Marina; Drousiotou, Anthi

    2014-12-01

    Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in β-hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside. We describe the first patient with Tay-Sachs disease in the Cypriot population, a juvenile case which presented with developmental regression at the age of five. The diagnosis was confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and fibroblasts. Sequencing the HEXA gene resulted in the identification of two previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the silent mutation c.1305C>T (p.=). The silent mutation was reported once before in a juvenile TSD patient of West Indian origin with an unusually mild phenotype. The presence of this mutation in another juvenile TSD patient provides further evidence that it is a disease-causing mutation. Successful preimplantation genetic diagnosis (PGD) and prenatal follow-up were provided to the couple.

  4. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus

    2007-01-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families......, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...... upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both...

  5. A new nonsense mutation in the NF1 gene with neurofibromatosis-Noonan syndrome phenotype.

    Science.gov (United States)

    Yimenicioğlu, Sevgi; Yakut, Ayten; Karaer, Kadri; Zenker, Martin; Ekici, Arzu; Carman, Kürşat Bora

    2012-12-01

    Neurofibromatosis-Noonan syndrome is a rare autosomal dominant disorder which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1 gene mutations are reported in the majority of these patients. Sequence analysis of the established genes for Noonan syndrome revealed no mutation; a heterozygous NF1 point mutation c.7549C>T in exon 51, creating a premature stop codon (p.R2517X), had been demonstrated. Neurofibromatosis-Noonan syndrome recently has been considered a subtype of NF1 and caused by different NF1 mutations. We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T in exon 51.

  6. Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.

    Science.gov (United States)

    Eisenkraft, Arik; Pode-Shakked, Ben; Goldstein, Nurit; Shpirer, Zvi; van Bokhoven, Hans; Anikster, Yair

    2015-01-01

    Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.

  7. A novel nonsense mutation in the tyrosinase gene is related to the albinism in a capuchin monkey (Sapajus apella).

    Science.gov (United States)

    Galante Rocha de Vasconcelos, Felipe Tadeu; Hauzman, Einat; Dutra Henriques, Leonardo; Kilpp Goulart, Paulo Roney; de Faria Galvão, Olavo; Sano, Ronaldo Yuiti; da Silva Souza, Givago; Lynch Alfaro, Jessica; de Lima Silveira, Luis Carlos; Fix Ventura, Dora; Oliveira Bonci, Daniela Maria

    2017-05-05

    Oculocutaneous Albinism (OCA) is an autosomal recessive inherited condition that affects the pigmentation of eyes, hair and skin. The OCA phenotype may be caused by mutations in the tyrosinase gene (TYR), which expresses the tyrosinase enzyme and has an important role in the synthesis of melanin pigment. The aim of this study was to identify the genetic mutation responsible for the albinism in a captive capuchin monkey, and to describe the TYR gene of normal phenotype individuals. In addition, we identified the subject's species. A homozygous nonsense mutation was identified in exon 1 of the TYR gene, with the substitution of a cytosine for a thymine nucleotide (C64T) at codon 22, leading to a premature stop codon (R22X) in the albino robust capuchin monkey. The albino and five non-albino robust capuchin monkeys were identified as Sapajus apella, based on phylogenetic analyses, pelage pattern and geographic provenance. One individual was identified as S. macrocephalus. We conclude that the point mutation C64T in the TYR gene is responsible for the OCA1 albino phenotype in the capuchin monkey, classified as Sapajus apella.

  8. A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism.

    Directory of Open Access Journals (Sweden)

    Naihong Yan

    Full Text Available BACKGROUND: The purpose of this study was to elucidate the molecular basis of ocular albinism type I in a Chinese pedigree. METHODOLOGY/PRINCIPAL FINDINGS: Complete ophthalmologic examinations were performed on 4 patients, 7 carriers and 17 unaffected individuals in this five-generation family. All coding exons of four-point-one (4.1, ezrin, radixin, moesin (FERM domain-containing 7 (FRMD7 and G protein-coupled receptor 143 (GPR143 genes were amplified by polymerase chain reaction (PCR, sequenced and compared with a reference database. Ocular albinism and nystagmus were found in all patients of this family. Macular hypoplasia was present in the patients including the proband. A novel nonsense hemizygous mutation c.807T>A in the GPR143 gene was identified in four patients and the heterozygous mutation was found in seven asymptomatic individuals. This mutation is a substitution of tyrosine for adenine which leads to a premature stop codon at position 269 (p.Y269X of GPR143. CONCLUSIONS/SIGNIFICANCE: This is the first report that p.Y269X mutation of GPR143 gene is responsible for the pathogenesis of familial ocular albinism. These results expand the mutation spectrum of GPR143, and demonstrate the clinical characteristics of ocular albinism type I in Chinese population.

  9. The Identification of High-pitched Sung Vowels in Sense and Nonsense Words by Professional Singers and Untrained Listeners.

    Science.gov (United States)

    Deme, Andrea

    2017-03-01

    High-pitched sung vowels may be considered phonetically "underspecified" because of (i) the tuning of the F 1 to the f 0 accompanying pitch raising and (ii) the wide harmonic spacing of the voice source resulting in the undersampling of the vocal tract transfer function. Therefore, sung vowel intelligibility is expected to decrease as the f 0 increases. Based on the literature of speech perception, it is often suggested that sung vowels are better perceived if uttered in consonantal (CVC) context than in isolation even at high f 0 . The results for singing, however, are contradictory. In the present study, we further investigate this question. We compare vowel identification in sense and nonsense CVC sequences and show that the positive effect of the context disappears if the number of legal choices in a perception test is similar in both conditions, meaning that any positive effect of the CVC context may only stem from the smaller number of possible responses, i.e., from higher probabilities. Additionally, it is also tested whether the training in production (i.e., singing training) may also lead to a perceptual advantage of the singers over nonsingers in the identification of high-pitched sung vowels. The results show no advantage of this kind. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. Novel nonsense mutation of the endothelin-B receptor gene in a family with Waardenburg-Hirschsprung disease.

    Science.gov (United States)

    Syrris, P; Carter, N D; Patton, M A

    1999-11-05

    Waardenburg syndrome (WS) comprises sensorineural hearing loss, hypopigmentation of skin and hair, and pigmentary disturbances of the irides. Four types of WS have been classified to date; in WS type IV (WS4), patients additionally have colonic aganglionosis (Hirschsprung disease, HSCR). Mutations in the endothelin-3 (EDN3), endothelin-B receptor (EDNRB), and Sox10 genes have been identified as causative for WS type IV. We screened a family with a combined WS-HSCR phenotype for mutations in the EDNRB locus using standard DNA mutation analysis and sequencing techniques. We have identified a novel nonsense mutation at codon 253 (CGA-->TGA, Arg-->STOP). This mutation leads to a premature end of the translation of EDNRB at exon 3, and it is predicted to produce a truncated and nonfunctional endothelin-B receptor. All affected relatives were heterozygous for the Arg(253)-->STOP mutation, whereas it was not observed in over 50 unrelated individuals used as controls. These data confirm the role of EDNRB in the cause of the Waardenburg-Hirschsprung syndrome and demonstrate that in WS-HSCR there is a lack of correlation between phenotype and genotype and a variable expression of disease even within the same family. Copyright 1999 Wiley-Liss, Inc.

  11. A novel homozygous stop-codon mutation in human HFE responsible for nonsense-mediated mRNA decay.

    Science.gov (United States)

    Padula, Maria Carmela; Martelli, Giuseppe; Larocca, Marilena; Rossano, Rocco; Olivieri, Attilio

    2014-09-01

    HFE-hemochromatosis (HH) is an autosomal disease characterized by excessive iron absorption. Homozygotes for H63D variant, and still less H63D heterozygotes, generally do not express HH phenotype. The data collected in our previous study in the province of Matera (Basilicata, Italy) underlined that some H63D carriers showed altered iron metabolism, without additional factors. In this study, we selected a cohort of 10/22 H63D carriers with severe biochemical iron overload (BIO). Additional analysis was performed for studying HFE exons, exon-intron boundaries, and untranslated regions (UTRs) by performing DNA extraction, PCR amplification and sequencing. The results showed a novel substitution (NM_000410.3:c.847C>T) in a patient exon 4 (GenBankJQ478433); it introduces a premature stop-codon (PTC). RNA extraction and reverse-transcription were also performed. Quantitative real-time PCR was carried out for verifying if our aberrant mRNA is targeted for nonsense-mediated mRNA decay (NMD); we observed that patient HFE mRNA was expressed much less than calibrator, suggesting that the mutated HFE protein cannot play its role in iron metabolism regulation, resulting in proband BIO. Our finding is the first evidence of a variation responsible for a PTC in iron cycle genes. The genotype-phenotype correlation observed in our cases could be related to the additional mutation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Insulin Signaling Augments eIF4E-Dependent Nonsense-Mediated mRNA Decay in Mammalian Cells.

    Science.gov (United States)

    Park, Jungyun; Ahn, Seyoung; Jayabalan, Aravinth K; Ohn, Takbum; Koh, Hyun Chul; Hwang, Jungwook

    2016-07-01

    Nonsense-mediated mRNA decay (NMD) modulates the level of mRNA harboring a premature termination codon (PTC) in a translation-dependent manner. Inhibition of translation is known to impair NMD; however, few studies have investigated the correlation between enhanced translation and increased NMD. Here, we demonstrate that insulin signaling events increase translation, leading to an increase in NMD of eIF4E-bound transcripts. We provide evidence that (i) insulin-mediated enhancement of translation augments NMD and rapamycin abrogates this enhancement; (ii) an increase in AKT phosphorylation due to inhibition of PTEN facilitates NMD; (iii) insulin stimulation increases the binding of up-frameshift factor 1 (UPF1), most likely to eIF4E-bound PTC-containing transcripts; and (iv) insulin stimulation induces the colocalization of UPF1 and eIF4E in processing bodies. These results illustrate how extracellular signaling promotes the removal of eIF4E-bound NMD targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.

    Science.gov (United States)

    Mallet, A; Kypriotou, M; George, K; Leclerc, E; Rivero, D; Mazereeuw-Hautier, J; Serre, G; Huber, M; Jonca, N; Hohl, D

    2013-12-01

    Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). To investigate a novel mutation in CDSN. A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional. © 2013 British Association of Dermatologists.

  14. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis.

    Science.gov (United States)

    Kwon, Young-Ju; Park, Mi-Jeong; Kim, Sang-Gyu; Baldwin, Ian T; Park, Chung-Mo

    2014-05-19

    The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5' splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress

  15. A nonsense mutation in TMEM95 encoding a nondescript transmembrane protein causes idiopathic male subfertility in cattle.

    Directory of Open Access Journals (Sweden)

    Hubert Pausch

    2014-01-01

    Full Text Available Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e., idiopathic subfertility. Artificial insemination (AI in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS. Imputed genotypes of 652,856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV population. Male reproductive ability (MRA was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08 × 10(-59. Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35,671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome re-sequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c.483C>A, p.Cys161X in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic

  16. A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle.

    Science.gov (United States)

    Koltes, James E; Mishra, Bishnu P; Kumar, Dinesh; Kataria, Ranjit S; Totir, Liviu R; Fernando, Rohan L; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M

    2009-11-17

    Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle.

  17. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis

    Science.gov (United States)

    2014-01-01

    Background The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. Results We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5′ splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Conclusion Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock

  18. The SMN1 common variant c.22 dupA in Chinese patients causes spinal muscular atrophy by nonsense-mediated mRNA decay in humans.

    Science.gov (United States)

    Bai, JinLi; Qu, YuJin; Cao, YanYan; Yang, Lan; Ge, Lin; Jin, YuWei; Wang, Hong; Song, Fang

    2018-02-20

    Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is mostly caused by homozygous deletion of the SMN1 gene. Approximately 5%-10% of SMA patients are believed to have SMN1 variants. c.22 dupA (p.Ser8lysfs*23) has been identified as the most frequent variant in the Chinese SMA population and to be associated with a severe phenotype. However, the exact molecular mechanism of the variant on the pathogenesis of SMA is unclear. We observed that SMN1 mRNA and the SMN protein in the peripheral blood cells of a patient with c.22 dupA were lower than those of controls. The aim of this study is to investigate whether nonsense-mediated mRNA decay (NMD) plays a role in the mechanism of the c.22 dupA variant of the SMN1 gene as it causes SMA. Two lymphoblasts cell lines from two patients (patient 1 and 2) with the c.22 dupA, and one dermal fibroblasts cell line from patient 2 were included in our study. Two-stage validation of the NMD mechanism was supplied. We first measured the changes in the transcript levels of the SMN1 gene by real-time quantitative PCR after immortalized B-lymphoblasts and dermal fibroblasts cells of the SMA patients were treated with inhibitors of the NMD pathway, including puromycin and cyclohemide. Next, lentivirus-mediated knockdown of the key NMD factor-Up-frameshift protein 1 (UPF1)-was performed in the fibroblasts cell line to further clarify whether the variant led to NMD, as UPF1 recognizes abnormally terminated transcripts as NMD substrates during translation. SC35 1.7-kb transcripts, a physiological NMD substrate was determined to be a NMD positive gene in our experiments. The two inhibitors resulted in a dramatic escalation of the levels of the full-length SMN1 (fl-SMN1) transcripts. Additionally, the SC35 1.7-kb mRNA levels were also increased, suggesting that NMD pathway is suppressed by the two inhibitors. For the 3 cell lines, the fold increase of the SMN1 transcript levels of cycloheximide ranged

  19. Inherited protein S deficiency due to a novel nonsense mutation in the PROS1 gene in the patient with recurrent vascular access thrombosis: A case report

    Directory of Open Access Journals (Sweden)

    Eun Jin Cho

    2012-03-01

    Full Text Available Vascular access thrombosis is one of the major causes of morbidity in patients maintained on chronic hemodialysis. Thrombophilia has been recognized as a risk factor of vascular access thrombosis. The authors report a case of inherited protein S deficiency associated with vascular access thrombotic events. DNA sequence analysis of the PROS1 gene identified a novel heterozygous nonsense mutation in exon 10 by transition of AAG (lysine to TAG (stop codon at codon 473 (c.1417A>T, p.K473X. Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients.

  20. MECHANISM AND REGULATION OF NONSENSE-MEDIATED MRNA DECAY (NMD, AN ESSENTIAL QUALITY CONTROL SYSTEM OF PLANTS

    Directory of Open Access Journals (Sweden)

    D. Silhavy

    2008-09-01

    Full Text Available In eukaryotic cell, various quality control mechanisms have evolved to ensure that only perfect mRNAs could be translated. Nonsense-mediated mRNA decay (NMD is a quality control system that identifies and eliminates mRNAs containing premature termination codons, thereby preventing the accumulation of potentially harmful truncated proteins. While NMD is well-characterized in yeast, in invertebrates and in mammals, plant NMD is poorly understood. In yeast and in invertebrates unusually long 3'untranslated regions (3'UTRs render an mRNA subject to NMD, while in mammals' 3'UTR located introns trigger NMD. UPF1, 2 and 3 are the key trans-acting NMD factors in yeast as well as in animals. However, in mammals, the core components of the Exon Junction Complex (Mago, Y14, eIF4A3 and MLN51 are also required for NMD. It was proposed that long 3’UTR-induced NMD is the ancient type and that it was changed to a more complex intron-based NMD in mammals. To better understand the evolution of eukaryotic NMD systems, we have studied the NMD machinery of plants, as plants are outgroup relative to fungi and animals. We have elaborated various transient assays to analyze plant NMD. Using these assays we defined the cis elements of plant NMD and characterized several trans-acting plant NMD factors. We demonstrated that two plant NMD pathways co-exist, one pathway, as yeast or invertebrate NMD systems, eliminates mRNAs with long 3'UTRs, while a distinct pathway, like mammalian NMD, degrades mRNAs harbouring 3'UTR-located introns. We showed that UPF1, UPF2, and SMG-7 are involved in both plant NMD pathways, whereas Mago and Y14 are required only for intron-based NMD. We also provide evidence that the molecular mechanism of long 3'UTR-based plant NMD resembles yeast NMD, while the intron-based NMD is similar to mammalian NMD. Moreover we have found that the SMG-7 component of plant NMD is targeted by NMD suggesting that plant NMD is autoregulated. We propose that in

  1. Quantum sense and nonsense

    CERN Document Server

    Bricmont, Jean

    2017-01-01

    Permeated by the author's delightful humor, this little book explains, with nearly no mathematics, the main conceptual issues associated with quantum mechanics:  The issue of determinism. Does quantum mechanics signify the end of a deterministic word-view?  The role of the human subject or of the "observer" in science. Since Copernicus, science has increasingly tended to dethrone Man from his formerly held special position in the Universe. But quantum mechanics, with its emphasis on the notion of observation, may once more have given a central role to the human subject.  The issue of locality. Does quantum mechanics imply that instantaneous actions at a distance exist in Nature? In these pages the author offers a variety of views and answers - bad as well as good - to these questions. The reader will be both entertained and enlightened by Jean Bricmont's clear and incisive arguments.

  2. A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10.

    Science.gov (United States)

    Suzuki, Noriomi; Mutai, Hideki; Miya, Fuyuki; Tsunoda, Tatsuhiko; Terashima, Hiroshi; Morimoto, Noriko; Matsunaga, Tatsuo

    2018-05-23

    Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10.

  3. VHL Frameshift Mutation as Target of Nonsense-Mediated mRNA Decay in Drosophila melanogaster and Human HEK293 Cell Line

    Directory of Open Access Journals (Sweden)

    Lucia Micale

    2009-01-01

    Full Text Available There are many well-studied examples of human phenotypes resulting from nonsense or frameshift mutations that are modulated by Nonsense-Mediated mRNA Decay (NMD, a process that typically degrades transcripts containing premature termination codons (PTCs in order to prevent translation of unnecessary or aberrant transcripts. Different types of germline mutations in the VHL gene cause the von Hippel-Lindau disease, a dominantly inherited familial cancer syndrome with a marked phenotypic variability and age-dependent penetrance. By generating the Drosophila UAS:Upf1D45B line we showed the possible involvement of NMD mechanism in the modulation of the c.172delG frameshift mutation located in the exon 1 of Vhl gene. Further, by Quantitative Real-time PCR (QPCR we demonstrated that the corresponding c.163delG human mutation is targeted by NMD in human HEK 293 cells. The UAS:Upf1D45B line represents a useful system to identify novel substrates of NMD pathway in Drosophila melanogaster. Finally, we suggest the possible role of NMD on the regulation of VHL mutations.

  4. Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and enhance exclusion of the mutant exon.

    Science.gov (United States)

    Musante, Luciana; Kunde, Stella-Amrei; Sulistio, Tina O; Fischer, Ute; Grimme, Astrid; Frints, Suzanna G M; Schwartz, Charles E; Martínez, Francisco; Romano, Corrado; Ropers, Hans-Hilger; Kalscheuer, Vera M

    2010-01-01

    The polyglutamine binding protein 1 (PQBP1) gene plays an important role in X-linked mental retardation (XLMR). Nine of the thirteen PQBP1 mutations known to date affect the AG hexamer in exon 4 and cause frameshifts introducing premature termination codons (PTCs). However, the phenotype in this group of patients is variable. To investigate the pathology of these PQBP1 mutations, we evaluated their consequences on mRNA and protein expression. RT-PCRs revealed mutation-specific reduction of PQBP1 mRNAs carrying the PTCs that can be partially restored by blocking translation, thus indicating a role for the nonsense-mediated mRNA decay pathway. In addition, these mutations resulted in altered levels of PQBP1 transcripts that skipped exon 4, probably as a result of altering important splicing motifs via nonsense-associated altered splicing (NAS). This hypothesis is supported by transfection experiments using wild-type and mutant PQBP1 minigenes. Moreover, we show that a truncated PQBP1 protein is indeed present in the patients. Remarkably, patients with insertion/deletion mutations in the AG hexamer express significantly increased levels of a PQBP1 isoform, which is very likely encoded by the transcripts without exon 4, confirming the findings at the mRNA level. Our study provides significant insight into the early events contributing to the pathogenesis of the PQBP1 related XLMR disease.

  5. Readthrough of long-QT syndrome type 1 nonsense mutations rescues function but alters the biophysical properties of the channel.

    Science.gov (United States)

    Harmer, Stephen C; Mohal, Jagdeep S; Kemp, Duncan; Tinker, Andrew

    2012-05-01

    The nonsense mutations R518X-KCNQ1 and Q530X-KCNQ1 cause LQT1 (long-QT syndrome type 1) and result in a complete loss of I(Ks) channel function. In the present study we attempted to rescue the function of these mutants, in HEK (human embryonic kidney)-293 cells, by promoting readthrough of their PTCs (premature termination codons) using the pharmacological agents G-418, gentamicin and PTC124. Gentamicin and G-418 acted to promote full-length channel protein expression from R518X at 100 μM and from Q530X at 1 mM. In contrast, PTC124 did not, at any dose tested, induce readthrough of either mutant. G-418 (1 mM) treatment also acted to significantly (Pbiophysical properties of the currents produced from R518X, while similar, were not identical with wild-type as the voltage-dependence of activation was significantly (P<0.05) shifted by +25 mV. Overall, these findings indicate that although functional rescue of LQT1 nonsense mutations is possible, it is dependent on the degree of readthrough achieved and the effect on channel function of the amino acid substituted for the PTC. Such considerations will determine the success of future therapies.

  6. [Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome].

    Science.gov (United States)

    Diniz, Erik Trovão; Jorge, Alexander A L; Arnhold, Ivo J P; Rosenbloom, Arlan L; Bandeira, Francisco

    2008-11-01

    To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. The patient had high GH (26 microg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.

  7. A nonsense mutation in the beta-carotene oxygenase 2 (BCO2 gene is tightly associated with accumulation of carotenoids in adipose tissue in sheep (Ovis aries

    Directory of Open Access Journals (Sweden)

    Boman Inger A

    2010-02-01

    Full Text Available Abstract Background Sheep carcasses with yellow fat are sporadically observed at Norwegian slaughter houses. This phenomenon is known to be inherited as a recessive trait, and is caused by accumulation of carotenoids in adipose tissue. Two enzymes are known to be important in carotenoid degradation in mammals, and are therefore potential candidate genes for this trait. These are beta-carotene 15,15'-monooxygenase 1 (BCMO1 and the beta-carotene oxygenase 2 (BCO2. Results In the present study the coding region of the BCMO1 and the BCO2 gene were sequenced in yellow fat individuals and compared to the corresponding sequences from control animals with white fat. In the yellow fat individuals a nonsense mutation was found in BCO2 nucleotide position 196 (c.196C>T, introducing a stop codon in amino acid position 66. The full length protein consists of 575 amino acids. In spite of a very low frequency of this mutation in the Norwegian AI-ram population, 16 out of 18 yellow fat lambs were found to be homozygous for this mutation. Conclusion In the present study a nonsense mutation (c.196C>T in the beta-carotene oxygenase 2 (BCO2 gene is found to strongly associate with the yellow fat phenotype in sheep. The existence of individuals lacking this mutation, but still demonstrating yellow fat, suggests that additional mutations may cause a similar phenotype in this population. The results demonstrate a quantitatively important role for BCO2 in carotenoid degradation, which might indicate a broad enzyme specificity for carotenoids. Animals homozygous for the mutation are not reported to suffer from any negative health or development traits, pointing towards a minor role of BCO2 in vitamin A formation. Genotyping AI rams for c.196C>T can now be actively used in selection against the yellow fat trait.

  8. Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

    Science.gov (United States)

    Simonelli, Francesca; Testa, Francesco; Zernant, Jana; Nesti, Anna; Rossi, Settimio; Rinaldi, Ernesto; Allikmets, Rando

    2004-01-01

    Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull's eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology. Copyright 2004 S. Karger AG, Basel

  9. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

    Science.gov (United States)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

    2011-11-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

  10. A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report.

    Science.gov (United States)

    Nishimura, Motoi; Ueda, Marehiko; Ebata, Ryota; Utsuno, Emi; Ishii, Takuma; Matsushita, Kazuyuki; Ohara, Osamu; Shimojo, Naoki; Kobayashi, Yoshio; Nomura, Fumio

    2017-06-08

    According to previous KCNQ1 (potassium channel, voltage gated, KQT-like subfamily, member 1) gene screening studies, missense variants, but not nonsense or frame-shift variants, cause the majority of long QT syndrome (LQTS; Romano-Ward syndrome [RWS]) 1 cases. Several missense variants are reported to cause RWS by a dominant-negative mechanism, and some KCNQ1 variants can cause both Jervell and Lange-Nielsen Syndrome (JLNS; in an autosomal recessive manner) and LQTS1 (in an autosomal dominant manner), while other KCNQ1 variants cause only JLNS. The human KCNQ1 gene is known to have two transcript isoforms (kidney isoform and pancreas isoform), and both isoforms can form a functional cardiac potassium channel. Here, we report a novel nonsense KCNQ1 variant causing not only JLNS, but also significant QTc prolongation identical to RWS in an autosomal dominant manner. Our case study supports that haploinsufficiency in the KCNQ1 gene is causative of significant QTc prolongation identical to RWS. Interestingly, the nonsense variant (NM_000218.2:c.115G > T [p.Glu39X]) locates in exon 1a of KCNQ1, which is a kidney-isoform specific exon. The variant is located closer to the N-terminus than previously identified nonsense or frame-shift variants. To the best of our knowledge, this is the first report showing that a nonsense variant in exon 1a of KCNQ1, which is the kidney-isoform specific exon, causes JLNS. Our findings may be informative to the genetic pathogenesis of RWS and JLNS caused by KCNQ1 variants.

  11. Anxiety Disorders

    Science.gov (United States)

    ... Registry Residents & Medical Students Residents Medical Students Patients & Families Mental Health Disorders/Substance Use Find a Psychiatrist Addiction and Substance Use Disorders ADHD Anxiety Disorders Autism Spectrum Disorder Bipolar Disorders Depression Eating Disorders Obsessive-Compulsive ...

  12. Mental Disorders

    Science.gov (United States)

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

  13. Schizoaffective disorder

    Science.gov (United States)

    ... or do not improve with treatment Thoughts of suicide or of harming others Alternative Names Mood disorder - schizoaffective disorder; Psychosis - schizoaffective disorder Images Schizoaffective disorder ...

  14. Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.

    Science.gov (United States)

    Zobor, Ditta; Balousha, Ghassan; Baumann, Britta; Wissinger, Bernd

    2014-01-01

    Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression

  15. Missense and nonsense mutations in melanocortin 1 receptor (MC1R gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences

    Directory of Open Access Journals (Sweden)

    Davoli Roberta

    2009-08-01

    Full Text Available Abstract Background Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals. Results The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals. Five single nucleotide polymorphisms (SNPs were identified: one nonsense mutation (p.Q225X, three missense mutations (p.A81V, p.F250V, and p.C267W, and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour. Conclusion According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic

  16. A Role for Nonsense-Mediated mRNA Decay in Plants: Pathogen Responses Are Induced in Arabidopsis thaliana NMD Mutants

    Science.gov (United States)

    Rayson, Samantha; Arciga-Reyes, Luis; Wootton, Lucie; De Torres Zabala, Marta; Truman, William; Graham, Neil; Grant, Murray; Davies, Brendan

    2012-01-01

    Nonsense-mediated mRNA decay (NMD) is a conserved mechanism that targets aberrant mRNAs for destruction. NMD has also been found to regulate the expression of large numbers of genes in diverse organisms, although the biological role for this is unclear and few evolutionarily conserved targets have been identified. Expression analyses of three Arabidopsis thaliana lines deficient in NMD reveal that the vast majority of NMD-targeted transcripts are associated with response to pathogens. Congruently, NMD mutants, in which these transcripts are elevated, confer partial resistance to Pseudomonas syringae. These findings suggest a biological rationale for the regulation of gene expression by NMD in plants and suggest that manipulation of NMD could offer a new approach for crop protection. Amongst the few non-pathogen responsive NMD-targeted genes, one potential NMD targeted signal, the evolutionarily conserved upstream open reading frame (CuORF), was found to be hugely over-represented, raising the possibility that this feature could be used to target specific physiological mRNAs for control by NMD. PMID:22384098

  17. A Novel Nonsense Variant in Nav1.5 Cofactor MOG1 Eliminates Its Sodium Current Increasing Effect and May Increase the Risk of Arrhythmias

    DEFF Research Database (Denmark)

    Olesen, Morten S; Jensen, Niels F; Holst, Anders G

    2011-01-01

    at a lower frequency (1.8% vs 0.4%, P = 0.078). Electrophysiological investigation showed that the p.E61X variant completely eliminates the sodium current-increasing effect of MOG1 and thereby causes loss of function in the sodium current. When mimicking heterozygosity by coexpression of Nav1.5 with wild......BACKGROUND: The protein MOG1 is a cofactor of the cardiac sodium channel, Nav1.5. Overexpression of MOG1 in Nav1.5-expressing cells increases sodium current markedly. Mutations in the genes encoding Nav1.5 and its accessory proteins have been associated with cardiac arrhythmias of significant...... and 23 were patients with Brugada syndrome. The effect of one variant was investigated functionally by patch-clamping CHO-K1 cells coexpressing Nav1.5 with MOG1. RESULTS: We uncovered a novel heterozygous nonsense variant, c.181G>T (p.E61X), that, however, was also present in control subjects, albeit...

  18. Acute intermittent porphyria: A single-base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide

    Energy Technology Data Exchange (ETDEWEB)

    Lee, G.L.; Astrin, K.H.; Desnick, R.J. [Mount Sinai School of Medicine, New York, NY (United States)

    1995-08-28

    Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, since the life-threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solid-phase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. 29 refs., 2 figs.

  19. mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    2017-11-01

    Full Text Available As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes. We analyzed mRNA processing in seven zebrafish lines with mutations expected to disrupt gene function, generated by CRISPR/Cas9 or ENU mutagenesis methods. Five of the seven lines showed evidence of altered mRNA processing: one through a skipped exon that did not lead to a frame shift, one through nonsense-associated splicing that did not lead to a frame shift, and three through the use of cryptic splice sites. These results highlight the need for a methodical analysis of the mRNA produced in mutant lines before making conclusions or embarking on studies that assume loss of function as a result of a given genomic change. Furthermore, recognition of the types of adaptations that can occur may inform the strategies of mutant generation.

  20. New evidence for the role of calpain 10 in autosomal recessive intellectual disability: identification of two novel nonsense variants by exome sequencing in Iranian families.

    Science.gov (United States)

    Oladnabi, Morteza; Musante, Luciana; Larti, Farzaneh; Hu, Hao; Abedini, Seyedeh Sedigheh; Wienker, Thomas; Ropers, Hans Hilger; Kahrizi, Kimia; Najmabadi, Hossein

    2015-03-01

    Knowledge of the genes responsible for intellectual disability, particularly autosomal recessive forms, is rapidly expanding. Increasing numbers of the gene show great heterogeneity and supports the hypothesis that human genome may contain over 2000 causative genes with a critical role in brain development. Since 2004, we have applied genome-wide SNP genotyping and next-generation sequencing in large consanguineous Iranian families with intellectual disability, to identify the genes harboring disease-causing mutations. The current study paved the way for identification of responsible genes in two unrelated Iranian families. We found two novel nonsense mutations, p.C77* and p.Q115*, in the calpain catalytic domain of CAPN10, which is a cysteine protease known to be involved in pathogenesis of noninsulin-dependent diabetes mellitus. Another different mutation in this gene (p.S138_R139ins5) has previously been reported in an Iranian family. All of these patients have common clinical features in spite of specific brain structural abnormalities on MRI. Different mutations in CAPN10 have already been found in three independent Iranian families. These results have strongly supported the possible role of CAPN10 in human brain development. Altogether, we proposed CAPN10 as a promising candidate gene for intellectual disability, which should be considered in diagnostic gene panels.

  1. FCJ-160 Politics is Serious Business: Jacques Rancière, Griefing, and the Re-Partitioning of the (NonSensical

    Directory of Open Access Journals (Sweden)

    Steve Holmes

    2013-12-01

    Full Text Available This article contextualises certain elements of ‘griefing’ as a form of political action in virtual world by drawing on the political philosophy of Jacques Rancière. A small but growing number of scholars are starting to view griefing as an avant-garde, anarchist, or hacktivist political activity. I suggest that Rancière offers a more specific articulation of what constitutes political action and activism for griefing collectives because his understanding of politics is entirely grounded in relationship to the types of communities and individual political equality. The article focuses specifically on the Patriotic Nigras activities in the Great Habbo Raid of 2006 in an attempt to understand how a Rancièreian framework can provide some analytical tools for articulating politics in virtual worlds. I conclude that the PN do not ultimately realise a Rancièreian framework. They challenge not partitions of the sensible, but partitions of the nonsensical specific to the different operation of politics and community formation in virtual worlds.

  2. RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.

    Science.gov (United States)

    Son, Heehwa G; Seo, Mihwa; Ham, Seokjin; Hwang, Wooseon; Lee, Dongyeop; An, Seon Woo A; Artan, Murat; Seo, Keunhee; Kaletsky, Rachel; Arey, Rachel N; Ryu, Youngjae; Ha, Chang Man; Kim, Yoon Ki; Murphy, Coleen T; Roh, Tae-Young; Nam, Hong Gil; Lee, Seung-Jae V

    2017-03-09

    Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.

  3. De novo SOX10 Nonsense Mutation in a Patient with Kallmann Syndrome, Deafness, Iris Hypopigmentation, and Hyperthyroidism.

    Science.gov (United States)

    Wang, Fang; Zhao, Shaoli; Xie, Yanhong; Yang, Wenjun; Mo, Zhaohui

    2018-03-01

    Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder characterized by hypogonadotropic hypogonadism and olfactory dysfunction. Recently, mutations in SOX10, a well-known causative gene of Waardenburg syndrome (WS), have been identified in a few KS patients with additional developmental defects including hearing loss. However, the understanding of SOX10 mutation associates with KS and other clinical consequences remains fragmentary. A 30-year-old Chinese male patient presented with no pubertal sex development when he was at the age of twelve years. Additionally, he showed anosmia, sensory deafness, and blue irises. Last year, he developed clinical symptoms of hyperthyroidism with a fast heartbeat, heat intolerance and weight loss. Blood examinations revealed low levels of FSH, LH, and testosterone. Thyroid function showed high levels of FT3, FT4 and extremely low level of TSH. Molecular analysis detected a de novo (c.565G>T/p.E189X) mutation in SOX10, which has previously been reported in a patient with WS4 (WS with Hirschsprung). The mutation was predicted to be probably damaging. These results highlight the significance of SOX10 haploinsufficiency as a genetic cause of KS. Importantly, our result implies that the same SOX10 mutation can underlie both typical KS and WS, while the correlation between SOX10 and hyperthyroidism still needs to be clarified in the future. © 2018 by the Association of Clinical Scientists, Inc.

  4. Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing.

    Science.gov (United States)

    Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Ingrassia, Valeria; Valenti, Vincenza; Giammanco, Antonina; Fayer, Francesca; Misiano, Gabriella; Cocorullo, Gianfranco; Scrimali, Chiara; Palesano, Ornella; Altieri, Grazia I; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

    Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL-10 mmol/L): 4 positive controls in whom pathogenic mutations had previously been identified by Sanger sequencing and 7 patients in whom the molecular defect was still unknown. The customized panel was accurate, and it allowed to confirm genetic variants previously identified in all positive controls with primary severe HTG. Only 1 patient of 7 with HTG was found to be carrier of a homozygous pathogenic mutation of the third novel mutation of LMF1 gene (c.1380C>G-p.Y460X). The clinical and molecular familial cascade screening allowed the identification of 2 additional affected siblings and 7 heterozygous carriers of the mutation. We showed that our targeted resequencing approach for genetic diagnosis of severe HTG appears to be accurate, less time consuming, and more economical compared with traditional Sanger resequencing. The identification of pathogenic mutations in candidate genes remains challenging and clinical resequencing should mainly intended for patients with strong clinical criteria for monogenic severe HTG. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. A non-sense mutation in the putative anti-mutator gene ada/alkA of Mycobacterium tuberculosis and M. bovis isolates suggests convergent evolution

    Directory of Open Access Journals (Sweden)

    Gicquel Brigitte

    2007-05-01

    Full Text Available Abstract Background Previous studies have suggested that variations in DNA repair genes of W-Beijing strains may have led to transient mutator phenotypes which in turn may have contributed to host adaptation of this strain family. Single nucleotide polymorphism (SNP in the DNA repair gene mutT1 was identified in MDR-prone strains from the Central African Republic. A Mycobacteriumtuberculosis H37Rv mutant inactivated in two DNA repair genes, namely ada/alkA and ogt, was shown to display a hypermutator phenotype. We then looked for polymorphisms in these genes in Central African Republic strains (CAR. Results In this study, 55 MDR and 194 non-MDR strains were analyzed. Variations in DNA repair genes ada/alkA and ogt were identified. Among them, by comparison to M. tuberculosis published sequences, we found a non-sense variation in ada/alkA gene which was also observed in M. bovis AF2122 strain. SNPs that are present in the adjacent regions to the amber variation are different in M. bovis and in M. tuberculosis strain. Conclusion An Amber codon was found in the ada/alkA locus of clustered M. tuberculosis isolates and in M. bovis strain AF2122. This is likely due to convergent evolution because SNP differences between strains are incompatible with horizontal transfer of an entire gene. This suggests that such a variation may confer a selective advantage and be implicated in hypermutator phenotype expression, which in turn contributes to adaptation to environmental changes.

  6. NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2.

    Directory of Open Access Journals (Sweden)

    B Kate Dredge

    Full Text Available Anti-NeuN (Neuronal Nuclei is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45-50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors, confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45-50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism.

  7. Two novel exonic point mutations in HEXA identified in a juvenile Tay-Sachs patient: role of alternative splicing and nonsense-mediated mRNA decay.

    Science.gov (United States)

    Levit, A; Nutman, D; Osher, E; Kamhi, E; Navon, R

    2010-06-01

    We have identified three mutations in the beta-hexoseaminidase A (HEXA) gene in a juvenile Tay-Sachs disease (TSD) patient, which exhibited a reduced level of HEXA mRNA. Two mutations are novel, c.814G>A (p.Gly272Arg) and c.1305C>T (p.=), located in exon 8 and in exon 11, respectively. The third mutation, c.1195A>G (p.Asn399Asp) in exon 11, has been previously characterized as a common polymorphism in African-Americans. Hex A activity measured in TSD Glial cells, transfected with HEXA cDNA constructs bearing these mutations, was unaltered from the activity level measured in normal HEXA cDNA. Analysis of RT-PCR products revealed three aberrant transcripts in the patient, one where exon 8 was absent, one where exon 11 was absent and a third lacking both exons 10 and 11. All three novel transcripts contain frameshifts resulting in premature termination codons (PTCs). Transfection of mini-gene constructs carrying the c.814G>A and c.1305C>T mutations proved that the two mutations result in exon skipping. mRNAs that harbor a PTC are detected and degraded by the nonsense-mediated mRNA decay (NMD) pathway to prevent synthesis of abnormal proteins. However, although NMD is functional in the patient's fibroblasts, aberrant transcripts are still present. We suggest that the level of correctly spliced transcripts as well as the efficiency in which NMD degrade the PTC-containing transcripts, apparently plays an important role in the phenotype severity of the unique patient and thus should be considered as a potential target for drug therapy.

  8. A nonsense mutation causing decreased levels of insulin receptor mRNA: Detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction

    International Nuclear Information System (INIS)

    Kadowaki, T.; Kadowaki, H.; Taylor, S.I.

    1990-01-01

    Mutations in the insulin receptor gene can render the cell resistant to the biological action of insulin. The authors have studied a patient with leprechaunism (leprechaun/Minn-1), a genetic syndrome associated with intrauterine growth retardation and extreme insulin resistance. Genomic DNA from the patient was amplified by the polymerase chain reaction catalyzed by Thermus aquaticus (Taq) DNA polymerase, and the amplified DNA was directly sequenced. A nonsense mutations was identified at codon 897 in exon 14 in the paternal allele of the patient's insulin receptor gene. Levels of insulin receptor mRNA are decreased to <10% of normal in Epstein-Barr virus-transformed lymphoblasts and cultured skin fibroblasts from this patient. Thus, this nonsense mutation appears to cause a decrease in the levels of insulin receptor mRNA. In addition, they have obtained indirect evidence that the patient's maternal allele of the insulin receptor gene contains a cis-acting dominant mutation that also decreases the level of mRNA, but by a different mechanism. The nucleotide sequence of the entire protein-coding domain and the sequences of the intron-exon boundaries for all 22 exons of the maternal allele were normal. Presumably, the mutation in the maternal allele maps elsewhere in the insulin receptor gene. Thus, they conclude that the patient is a compound heterozygote for two cis-acting dominant mutations in the insulin receptor gene: (i) a nonsense mutation in the paternal allel that reduces the level of insulin receptor mRNA and (ii) an as yet unidentified mutation in the maternal allele that either decreases the rate of transcription or decreases the stability of the mRNA

  9. Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS1R gene in three unrelated families.

    Science.gov (United States)

    Demirbilek, Huseyin; Ozbek, M Nuri; Demir, Korcan; Kotan, L Damla; Cesur, Yasar; Dogan, Murat; Temiz, Fatih; Mengen, Eda; Gurbuz, Fatih; Yuksel, Bilgin; Topaloglu, A Kemal

    2015-03-01

    The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, KISS1R mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism. Clinical characteristics, hormonal studies and genetic analyses of seven cases with idiopathic normosmic hypogonadotropic hypogonadism (nIHH) from three unrelated consanguineous families are presented. One male presented with absence of pubertal onset and required surgery for severe penoscrotal hypospadias and cryptorchidism, while other two males had absence of pubertal onset. Two of four female cases required replacement therapy for pubertal onset and maintenance, whereas the other two had spontaneous pubertal onset but incomplete maturation. In sequence analysis, we identified a novel homozygous nonsense (p.Y323X) mutation (c.C969A) in the last exon of the KISS1R gene in all clinically affected cases. We identified a homozygous nonsense mutation in the KISS1R gene in three unrelated families with nIHH, which enabled us to observe the phenotypic consequences of this rare condition. Escape from nonsense-mediated decay, and thus production of abnormal proteins, may account for the variable severity of the phenotype. Although KISS1R mutations are extremely rare and can cause a heterogeneous phenotype, analysis of the KISS1R gene should be a part of genetic analysis of patients with nIHH, to allow better understanding of phenotype-genotype relationship of KISS1R mutations and the underlying genetic basis of patients with nIHH. © 2014 John Wiley & Sons Ltd.

  10. Tay-Sachs disease in an Arab family due to c.78G>A HEXA nonsense mutation encoding a p.W26X early truncation enzyme peptide.

    Science.gov (United States)

    Haghighi, Alireza; Masri, Amira; Kornreich, Ruth; Desnick, Robert J

    2011-12-01

    Tay-Sachs disease (TSD), a pan-ethnic, autosomal recessive, neurodegenerative, lysosomal disease, results from deficient β-hexosaminidase A activity due to β-hexosaminidase α-subunit (HEXA) mutations. Prenatal/premarital carrier screening programs in the Ashkenazi Jewish community have markedly reduced disease occurrence. We report the first Jordanian Arab TSD patient diagnosed by deficient β-hexosaminidase A activity. HEXA mutation analysis revealed homozygosity for a nonsense mutation, c.78G>A (p.W26X). Previously reported in Arab patients, this mutation is a candidate for TSD screening in Arab populations. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Eating Disorders

    Science.gov (United States)

    ... of-control eating Women are more likely than men to have eating disorders. They usually start in the teenage years and often occur along with depression, anxiety disorders, and substance abuse. Eating disorders can ...

  12. Eating Disorders

    Science.gov (United States)

    ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home Research ... About Eating Disorders More Publications About Eating Disorders Research Results PubMed: Journal Articles about Eating Disorders Contact Us The National ...

  13. Personality Disorders

    Science.gov (United States)

    ... Disorders in Adults Data Sources Share Personality Disorders Definitions Personality disorders represent “an enduring pattern of inner ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  14. Schizoaffective Disorder

    Science.gov (United States)

    ... variations in brain chemistry and structure. Risk factors Factors that increase the risk of developing schizoaffective disorder include: Having a close blood relative who has schizoaffective disorder, schizophrenia or bipolar disorder Stressful events that trigger symptoms ...

  15. Independent inactivation of arginine decarboxylase genes by nonsense and missense mutations led to pseudogene formation in Chlamydia trachomatis serovar L2 and D strains

    Directory of Open Access Journals (Sweden)

    Graham David E

    2009-07-01

    Full Text Available Abstract Background Chlamydia have reduced genomes that reflect their obligately parasitic lifestyle. Despite their different tissue tropisms, chlamydial strains share a large number of common genes and have few recognized pseudogenes, indicating genomic stability. All of the Chlamydiaceae have homologs of the aaxABC gene cluster that encodes a functional arginine:agmatine exchange system in Chlamydia (Chlamydophilapneumoniae. However, Chlamydia trachomatis serovar L2 strains have a nonsense mutation in their aaxB genes, and C. trachomatis serovar A and B strains have frameshift mutations in their aaxC homologs, suggesting that relaxed selection may have enabled the evolution of aax pseudogenes. Biochemical experiments were performed to determine whether the aaxABC genes from C. trachomatis strains were transcribed, and mutagenesis was used to identify nucleotide substitutions that prevent protein maturation and activity. Molecular evolution techniques were applied to determine the relaxation of selection and the scope of aax gene inactivation in the Chlamydiales. Results The aaxABC genes were co-transcribed in C. trachomatis L2/434, during the mid-late stage of cellular infection. However, a stop codon in the aaxB gene from this strain prevented the heterologous production of an active pyruvoyl-dependent arginine decarboxylase. Replacing that ochre codon with its ancestral tryptophan codon rescued the activity of this self-cleaving enzyme. The aaxB gene from C. trachomatis D/UW-3 was heterologously expressed as a proenzyme that failed to cleave and form the catalytic pyruvoyl cofactor. This inactive protein could be rescued by replacing the arginine-115 codon with an ancestral glycine codon. The aaxC gene from the D/UW-3 strain encoded an active arginine:agmatine antiporter protein, while the L2/434 homolog was unexpectedly inactive. Yet the frequencies of nonsynonymous versus synonymous nucleotide substitutions show no signs of relaxed

  16. Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens

    Directory of Open Access Journals (Sweden)

    Wells Kirsty L

    2012-06-01

    Full Text Available Abstract Background Scaleless (sc/sc chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers, we mapped and identified the sc mutation. Results Through a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles. Conclusions This work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to

  17. Dyslipidemia, sense, antisense or nonsense?

    NARCIS (Netherlands)

    Visser, M.E.

    2011-01-01

    Maartje Visser onderzocht het remmen van de synthese van apoB met behulp van antisense - een nieuwe farmacologische techniek. Dit blijkt het slechte LDL-cholesterol op een effectieve manier te verlagen. Bij sommige proefpersonen resulteerde dit in leververvetting. Of dit op de lange termijn

  18. Somatic symptom disorder

    Science.gov (United States)

    ... related disorders; Somatization disorder; Somatiform disorders; Briquet syndrome; Illness anxiety disorder References American Psychiatric Association. Somatic symptom disorder. Diagnostic and Statistical Manual of Mental Disorders . ...

  19. Anxiety Disorders

    Science.gov (United States)

    ... the death of a loved one or parents' divorce) and major life transitions (like moving to a ... Ways to Deal With Anxiety Dealing With Difficult Emotions Anxiety Disorders Posttraumatic Stress Disorder Fears and Phobias ...

  20. Bipolar Disorder

    Science.gov (United States)

    Bipolar disorder is a serious mental illness. People who have it go through unusual mood changes. They go ... The down feeling is depression. The causes of bipolar disorder aren't always clear. It runs in families. ...

  1. Mathematics disorder

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001534.htm Mathematics disorder To use the sharing features on this page, please enable JavaScript. Mathematics disorder is a condition in which a child's ...

  2. Personality Disorders

    Science.gov (United States)

    Personality disorders are a group of mental illnesses. They involve long-term patterns of thoughts and behaviors ... serious problems with relationships and work. People with personality disorders have trouble dealing with everyday stresses and ...

  3. Cephalic Disorders

    Science.gov (United States)

    ... destructive lesions, but are sometimes the result of abnormal development. The disorder can occur before or after birth. Porencephaly most ... decade of life. SCHIZENCEPHALY is a rare developmental disorder characterized by abnormal slits, or clefts, in the cerebral hemispheres. Schizencephaly ...

  4. Oppositional defiant disorder

    Science.gov (United States)

    ... as possibilities: Anxiety disorders Attention-deficit/hyperactivity disorder (ADHD) Bipolar disorder Depression Learning disorders Substance abuse disorders Treatment The best treatment for the child is to ...

  5. Panic Disorder and Women

    Science.gov (United States)

    ... health illnesses Alcoholism, substance abuse, and addictive behavior Anxiety disorders Attention deficit hyperactivity disorder Bipolar disorder (manic depressive illness) Borderline personality disorder Depression Eating disorders Post-traumatic ...

  6. Eating Disorders

    OpenAIRE

    Gucciardi, Enza; Celasun, Nalan; Ahmad, Farah; Stewart, Donna E

    2004-01-01

    Abstract Health Issue Eating disorders are an increasing public health problem among young women. Anorexia and bulimia may give rise to serious physical conditions such as hypothermia, hypotension, electrolyte imbalance, endocrine disorders, and kidney failure. Key Issues Eating disorders are primarily a problem among women. In Ontario in 1995, over 90% of reported hospitalized cases of anorexia and bulimia were women. In addition to eating disorders, preoccupation with weight, body image and...

  7. A critical role for glycine transporters in hyperexcitability disorders

    Directory of Open Access Journals (Sweden)

    Robert J Harvey

    2008-03-01

    Full Text Available Defects in mammalian glycinergic neurotransmission result in a complex motor disorder characterized by neonatal hypertonia and an exaggerated startle refl ex, known as hyperekplexia (OMIM 149400. This affects newborn children and is characterized by noise or touch-induced seizures that result in muscle stiffness and breath-holding episodes. Although rare, this disorder can have serious consequences, including brain damage and/or sudden infant death. The primary cause of hyperekplexia is missense and nonsense mutations in the glycine receptor (GlyR α1 subunit gene (GLRA1 on chromosome 5q33.1, although we have also discovered rare mutations in the genes encoding the GlyR β subunit (GLRB and the GlyR clustering proteins gephyrin (GPNH and collybistin (ARHGEF9. Recent studies of the Na+ /Cl--dependent glycine transporters GlyT1 and GlyT2 using mouse knockout models and human genetics have revealed that mutations in GlyT2 are a second major cause of hyperekplexia, while the phenotype of the GlyT1 knockout mouse resembles a devastating neurological disorder known as glycine encephalopathy (OMIM 605899. These findings highlight the importance of these transporters in regulating the levels of synaptic glycine.

  8. Bipolar Disorder.

    Science.gov (United States)

    Spearing, Melissa

    Bipolar disorder, a brain disorder that causes unusual shifts in a person's mood, affects approximately one percent of the population. It commonly occurs in late adolescence and is often unrecognized. The diagnosis of bipolar disorder is made on the basis of symptoms, course of illness, and when possible, family history. Thoughts of suicide are…

  9. Speech disorders - children

    Science.gov (United States)

    ... disorder; Voice disorders; Vocal disorders; Disfluency; Communication disorder - speech disorder; Speech disorder - stuttering ... evaluation tools that can help identify and diagnose speech disorders: Denver Articulation Screening Examination Goldman-Fristoe Test of ...

  10. Nonsense and sense suppression abilities of original and derivative Methanosarcina mazei pyrrolysyl-tRNA synthetase-tRNA(Pyl pairs in the Escherichia coli BL21(DE3 cell strain.

    Directory of Open Access Journals (Sweden)

    Keturah A Odoi

    Full Text Available Systematic studies of nonsense and sense suppression of the original and three derivative Methanosarcina mazei PylRS-tRNA(Pyl pairs and cross recognition between nonsense codons and various tRNA(Pyl anticodons in the Escherichia coli BL21(DE3 cell strain are reported. tRNA(CUA(Pyl is orthogonal in E. coli and able to induce strong amber suppression when it is co-expressed with pyrrolysyl-tRNA synthetase (PylRS and charged with a PylRS substrate, N(ε-tert-butoxycarbonyl-L-lysine (BocK. Similar to tRNA(CUA(Pyl, tRNA(UUA(Pyl is also orthogonal in E. coli and can be coupled with PylRS to genetically incorporate BocK at an ochre mutation site. Although tRNA(UUA(Pyl is expected to recognize a UAG codon based on the wobble hypothesis, the PylRS-tRNA(UUA(Pyl pair does not give rise to amber suppression that surpasses the basal amber suppression level in E. coli. E. coli itself displays a relatively high opal suppression level and tryptophan (Trp is incorporated at an opal mutation site. Although the PylRS-tRNA(UCA(Pyl pair can be used to encode BocK at an opal codon, the pair fails to suppress the incorporation of Trp at the same site. tRNA(CCU(Pyl fails to deliver BocK at an AGG codon when co-expressed with PylRS in E. coli.

  11. Bipolar disorders

    DEFF Research Database (Denmark)

    Vieta, Eduard; Berk, Michael; Schulze, Thomas G

    2018-01-01

    Bipolar disorders are chronic and recurrent disorders that affect >1% of the global population. Bipolar disorders are leading causes of disability in young people as they can lead to cognitive and functional impairment and increased mortality, particularly from suicide and cardiovascular disease...... and accurate diagnosis is difficult in clinical practice as the onset of bipolar disorder is commonly characterized by nonspecific symptoms, mood lability or a depressive episode, which can be similar in presentation to unipolar depression. Moreover, patients and their families do not always understand...... a bipolar disorder from other conditions. Optimal early treatment of patients with evidence-based medication (typically mood stabilizers and antipsychotics) and psychosocial strategies is necessary....

  12. Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene.

    NARCIS (Netherlands)

    Muchir, A.; Engelen, B.G.M. van; Lammens, M.M.Y.; Mislow, J.M.; McNally, E.; Schwartz, K.; Bonne, G.

    2003-01-01

    Mutations in the LMNA gene encoding nuclear lamins A and C are responsible for seven inherited disorders affecting specific tissues. We have analyzed skin fibroblasts from a patient with type 1B limb-girdle muscular dystrophy and from her deceased newborn grandchild carrying, respectively, a

  13. A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

    Science.gov (United States)

    2014-01-01

    Background A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder. Methods Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer. Results DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*). Conclusions Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals. PMID:24571530

  14. Mental disorders, brain disorders, neurodevelopmental disorders ...

    African Journals Online (AJOL)

    . Amongst DSM's most vocal 'insider' critics has been Thomas Insel, Director of the US National Institute of Mental Health. Insel has publicly criticised DSM's adherence to a symptom-based classification of mental disorder, and used the weight ...

  15. [Eating disorders].

    Science.gov (United States)

    Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

    2015-02-01

    Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

  16. Cephalic Disorders

    Science.gov (United States)

    ... information sheet compiled by the National Institute of Neurological Disorders and Stroke (NINDS). Patient Organizations Birth Defect Research for Children, Inc. 976 Lake Baldwin Lane Suite 104 Orlando ...

  17. Conduct disorders

    NARCIS (Netherlands)

    Buitelaar, J.K.; Smeets, K.C.; Herpers, P.; Scheepers, F.; Glennon, J.; Rommelse, N.N.J.

    2013-01-01

    Conduct disorder (CD) is a frequently occurring psychiatric disorder characterized by a persistent pattern of aggressive and non-aggressive rule breaking antisocial behaviours that lead to considerable burden for the patients themselves, their family and society. This review paper updates diagnostic

  18. Personality disorders

    NARCIS (Netherlands)

    van den Bosch, L.M.C.; Verheul, R.; Verster, J.C.; Brady, K.; Galanter, M.; Conrod, P.

    2012-01-01

    Subject of this chapter is the often found combination of personality disorders and ­substance abuse disorders. The serious nature of this comorbidity is shown through the discussion of prevalence and epidemiological data. Literature shows that the comorbidity, hampering the diagnostic process, is

  19. Personality disorder

    DEFF Research Database (Denmark)

    Tyrer, Peter; Mulder, Roger; Crawford, Mike

    2010-01-01

    and to society, and interferes, usually negatively, with progress in the treatment of other mental disorders. We now have evidence that personality disorder, as currently classified, affects around 6% of the world population, and the differences between countries show no consistent variation. We are also getting......Personality disorder is now being accepted as an important condition in mainstream psychiatry across the world. Although it often remains unrecognized in ordinary practice, research studies have shown it is common, creates considerable morbidity, is associated with high costs to services...... increasing evidence that some treatments, mainly psychological, are of value in this group of disorders. What is now needed is a new classification that is of greater value to clinicians, and the WPA Section on Personality Disorders is currently undertaking this task....

  20. Gambling disorders.

    Science.gov (United States)

    Hodgins, David C; Stea, Jonathan N; Grant, Jon E

    2011-11-26

    Gambling disorders, including pathological gambling and problem gambling, have received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. This Seminar reviews prevalence, causes and associated features, screening and diagnosis, and treatment approaches. Gambling disorders affect 0·2-5·3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favourably evaluated, such as cognitive behavioural and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Autism spectrum disorder - childhood disintegrative disorder

    Science.gov (United States)

    ... part of the larger developmental disorder category of autism spectrum disorder . ... American Psychiatric Association. Autism spectrum disorder. ... VA: American Psychiatric Publishing: 2013;50-59. Raviola GJ, ...

  2. [Dissociative disorders and affective disorders].

    Science.gov (United States)

    Montant, J; Adida, M; Belzeaux, R; Cermolacce, M; Pringuey, D; Da Fonseca, D; Azorin, J-M

    2014-12-01

    The phenomenology of dissociative disorders may be complex and sometimes confusing. We describe here two cases who were initially misdiagnosed. The first case concerned a 61 year-old woman, who was initially diagnosed as an isolated dissociative fugue and was actually suffering from severe major depressive episode. The second case concerned a 55 year-old man, who was suffering from type I bipolar disorder and polyvascular disease, and was initially diagnosed as dissociative fugue in a mooddestabilization context, while it was finally a stroke. Yet dissociative disorders as affective disorder comorbidity are relatively unknown. We made a review on this topic. Dissociative disorders are often studied through psycho-trauma issues. Litterature is rare on affective illness comorbid with dissociative disorders, but highlight the link between bipolar and dissociative disorders. The later comorbidity often refers to an early onset subtype with also comorbid panic and depersonalization-derealization disorder. Besides, unipolar patients suffering from dissociative symptoms have more often cyclothymic affective temperament. Despite the limits of such studies dissociative symptoms-BD association seems to correspond to a clinical reality and further works on this topic may be warranted. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  3. Meeting Disorders.

    Science.gov (United States)

    Yager, Joel; Katzman, Jeffrey W

    2017-12-01

    Although meetings are central to organizational work, considerable time devoted to meetings in Academic Health Centers appears to be unproductively spent. The primary purposes of this article are to delineate and describe Meeting Disorders, pathological processes resulting in these inefficient and ineffective scenarios, and Meeting Fatigue Disorder (MFD), a clinical syndrome. The paper also offers preliminary approaches to remedies. The authors integrate observations made during tens of thousands of hours in administrative meetings in academic medical settings with information in the literature regarding the nature, causes and potential interventions for dysfunctional groups and meetings. Meeting Disorders, resulting from distinct pathologies of leadership and organization, constitute prevalent subgroups of the bureaucrapathologies, pathological conditions caused by dysfunctional bureaucratic processes that generate excesses of wasted time, effort, and other resources. These disorders also generate frustration and demoralization among participants, contributing to professional burnout. Meeting Fatigue Disorder (MFD) is a subjective condition that develops in individuals who overdose on these experiences and may reflect one manifestation of burnout. Meeting disorders and Meeting Fatigue Disorder occur commonly in bureaucratic life. Resources and potential remedies are available to help ameliorate their more deleterious effects.

  4. A Novel CACNA1A Nonsense Variant [c.4054C>T (p.Arg1352⁎] Causing Episodic Ataxia Type 2

    Directory of Open Access Journals (Sweden)

    Sean Lance

    2018-01-01

    Full Text Available Episodic ataxia is a heterogenous group of uncommon neurological disorders characterised by recurrent episodes of vertigo, dysarthria, and ataxia for which a variety of different genetic variations have been implicated. Episodic ataxia type two (EA2 is the most common and also has the largest number of identified causative genetic variants. Treatment with acetazolamide is effective in improving symptoms, so accurate diagnosis is essential. However, a large proportion of patients with EA2 have negative genetic testing. We present a patient with a typical history of EA2 who had a novel variant in the CACNA1A gene not previously described. Report of such variations is important in learning more about the disease and improving diagnostic yield for the patient.

  5. A Novel CACNA1A Nonsense Variant [c.4054C>T (p.Arg1352⁎)] Causing Episodic Ataxia Type 2.

    Science.gov (United States)

    Lance, Sean; Mossman, Stuart; Poke, Gemma

    2018-01-01

    Episodic ataxia is a heterogenous group of uncommon neurological disorders characterised by recurrent episodes of vertigo, dysarthria, and ataxia for which a variety of different genetic variations have been implicated. Episodic ataxia type two (EA2) is the most common and also has the largest number of identified causative genetic variants. Treatment with acetazolamide is effective in improving symptoms, so accurate diagnosis is essential. However, a large proportion of patients with EA2 have negative genetic testing. We present a patient with a typical history of EA2 who had a novel variant in the CACNA1A gene not previously described. Report of such variations is important in learning more about the disease and improving diagnostic yield for the patient.

  6. Conduct disorder

    Science.gov (United States)

    ... develop problems with drug abuse and the law. Depression and bipolar disorder may develop in the teen years and early adulthood. Suicide and violence toward others are also possible complications.

  7. Sleep Disorders

    Science.gov (United States)

    ... the day, even if you have had enough sleep? You might have a sleep disorder. The most common kinds are Insomnia - a hard time falling or staying asleep Sleep apnea - breathing interruptions during sleep Restless legs syndrome - ...

  8. Eating Disorders

    Science.gov (United States)

    ... to control them. Avoidant/Restrictive Food Intake Disorder (ARFID) ARFID is a new term that some people think ... eating issues can also cause it. People with ARFID don't have anorexia or bulimia, but they ...

  9. Neurocutaneous Disorders.

    Science.gov (United States)

    Rosser, Tena

    2018-02-01

    This article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common neurocutaneous disorders encountered in clinical adult and pediatric neurology practices. The phakomatoses are a phenotypically and genetically diverse group of multisystem disorders that primarily affect the skin and central nervous system. A greater understanding of the genetic and biological underpinnings of numerous neurocutaneous disorders has led to better clinical characterization, more refined diagnostic criteria, and improved treatments in neurofibromatosis type 1, Legius syndrome, neurofibromatosis type 2, Noonan syndrome with multiple lentigines, tuberous sclerosis complex, Sturge-Weber syndrome, and incontinentia pigmenti. Neurologists require a basic knowledge of and familiarity with a wide variety of neurocutaneous disorders because of the frequent involvement of the central and peripheral nervous systems. A simple routine skin examination can often open a broad differential diagnosis and lead to improved patient care.

  10. Factitious Disorder

    Science.gov (United States)

    ... support their claims. Factitious disorder signs and symptoms may include: Clever and convincing medical or psychological problems Extensive knowledge of medical terms and diseases Vague or inconsistent symptoms Conditions that get worse for no apparent ...

  11. Neuromuscular Disorders

    Science.gov (United States)

    ... lead to twitching, cramps, aches and pains, and joint and movement problems. Sometimes it also affects heart function and your ability to breathe. Examples of neuromuscular disorders include Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia ...

  12. Conduct Disorder

    Science.gov (United States)

    ... objections runs away from home often truant from school Children who exhibit these behaviors should receive a comprehensive evaluation by an experience mental health professional. Many children with a conduct disorder may ...

  13. Amnestic Disorders

    NARCIS (Netherlands)

    Kessels, R.P.C.; Savage, G.; Cautin, R.L.; Lilienfeld, S.O.

    2015-01-01

    Amnestic disorders may involve deficits in the encoding or storage of information in memory, or in retrieval of information from memory. Etiologies vary and include traumatic brain injury, neurodegenerative disease, and psychiatric illness. Different forms of amnesia can be distinguished:

  14. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    mediates circadian regulation of sleep. Misalignment with the rhythm of the sun results in circadian disorders and jet lag. The molecular basis of homeostatic sleep regulation is mostly unknown. A network of mutually inhibitory brain nuclei regulates sleep states and sleep-wake transitions. Abnormalities...... in these networks create sleep disorders, including rapid eye movement sleep behavior disorder, sleep walking, and narcolepsy. Physiological changes associated with sleep can be imbalanced, resulting in excess movements such as periodic leg movements during sleep or abnormal breathing in obstructive sleep apneas....... As every organ in the body is affected by sleep directly or indirectly, sleep and sleep-associated disorders are frequent and only now starting to be understood....

  15. TMJ Disorders

    Science.gov (United States)

    ... Aching pain in and around your ear Difficulty chewing or pain while chewing Aching facial pain Locking of the joint, making ... disorder. When to see a doctor Seek medical attention if you have persistent pain or tenderness in ...

  16. Autoimmune disorders

    Science.gov (United States)

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  17. Eating disorders

    OpenAIRE

    Kontić Olga; Vasiljević Nadja; Trišović Marija; Jorga Jagoda; Lakić Aneta; Jašović-Gašić Miroslava

    2012-01-01

    Eating disorders are considered chronic diseases of civilization. The most studied and well known are anorexia and bulimia nervosa. Anorexia is considered one of the most common psychiatric problems of girls in puberty and adolescence. Due to high mortality and morbidity as well as the increasing expansion of these diseases, it is clear why the amount of research on these diseases is growing worldwide. Eating disorders lead to numerous medical complications, mostly due to late diagnosis...

  18. The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis

    KAUST Repository

    Cui, Peng

    2016-02-18

    © 2016 American Society of Plant Biologists. All rights reserved. Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation-termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana. Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII. This dephosphorylation retains eIF4AIII in the nucleus and limits its accumulation in the cytoplasm. By analyzing RNA-seq data combined with quantitative RT-PCR validation, we found that a subset of alternatively spliced transcripts and 59-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant, cycloheximidetreated wild type, and upf3 mutant plants, indicating that FRY2 is essential for the degradation of these NMD transcripts.

  19. The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis

    KAUST Repository

    Cui, Peng; Chen, Tao; Qin, Tao; Ding, Feng; Wang, Zhenyu; Chen, Hao; Xiong, Liming

    2016-01-01

    © 2016 American Society of Plant Biologists. All rights reserved. Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation-termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana. Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII. This dephosphorylation retains eIF4AIII in the nucleus and limits its accumulation in the cytoplasm. By analyzing RNA-seq data combined with quantitative RT-PCR validation, we found that a subset of alternatively spliced transcripts and 59-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant, cycloheximidetreated wild type, and upf3 mutant plants, indicating that FRY2 is essential for the degradation of these NMD transcripts.

  20. Clinicopathological and Targeted Exome Gene Features of a Patient with Metastatic Acinic Cell Carcinoma of the Parotid Gland Harboring an ARID2 Nonsense Mutation and CDKN2A/B Deletion

    Directory of Open Access Journals (Sweden)

    Wayne A. Warner

    2015-01-01

    Full Text Available We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC. A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+, CD56 (−, and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor.

  1. Oppositional Defiant Disorder (ODD)

    Science.gov (United States)

    ... Antisocial behavior Impulse control problems Substance use disorder Suicide Many children and teens with ODD also have other mental health disorders, such as: Attention-deficit/hyperactivity disorder (ADHD) Conduct disorder Depression Anxiety Learning and communication disorders Treating these other ...

  2. Tic disorders.

    Science.gov (United States)

    Martino, Davide; Mink, Jonathan W

    2013-10-01

    Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders. Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery. The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.

  3. Digested disorder

    Science.gov (United States)

    DeForte, Shelly; Reddy, Krishna D; Uversky, Vladimir N

    2013-01-01

    The current literature on intrinsically disordered proteins is overwhelming. To keep interested readers up to speed with this literature, we continue a “Digested Disorder” project and represent a series of reader’s digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the period of April, May, and June of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings. PMID:28516028

  4. Digested disorder

    Science.gov (United States)

    Reddy, Krishna D; DeForte, Shelly; Uversky, Vladimir N

    2014-01-01

    The current literature on intrinsically disordered proteins grows fast. To keep interested readers up to speed with this literature, we continue a “Digested Disorder” project and represent a new issue of reader’s digest of the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the third quarter of 2013; i.e., during the period of June, July, and September of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings. PMID:28232877

  5. Movement disorders

    International Nuclear Information System (INIS)

    Leenders, K.L.

    1986-01-01

    This thesis describes the measurement of brain-tissue functions in patients with movement disorders using positron emission tomography (PET). This scanning technique is a method for direct in vivo quantitation of the regional tissue content of positron emitting radionuclides in brain (or other organs) in an essentially non-invasive way. Ch. 2 outlines some general features of PET and describes the scanner which has been used for the studies in this thesis. Also the tracer methodology, as applied to data investigations of movement disorders, are discussed. Ch. 3 contains the results of the PET investigations which were performed in the study of movement disorders. The results are presented in the form of 12 papers. The main goals of these studies were the understanding of the pathophysiology of Parkinson's disease, Huntington's chorea, Steele-Richardson-Olzewski syndrome and special case reports. Ch. 4 summarizes the results of these publications and Ch. 5 concludes the main part of this thesis with a general discussion of movement disorders in relation to PET investigations. 697 refs.; 60 figs.; 31 tabs

  6. Penis Disorders

    Science.gov (United States)

    Problems with the penis can cause pain and affect a man's sexual function and fertility. Penis disorders include Erectile dysfunction - inability to get or ... not go away Peyronie's disease - bending of the penis during an erection due to a hard lump ...

  7. Bipolar Disorder

    Science.gov (United States)

    ... one or other traumatic event Drug or alcohol abuse Complications Left untreated, bipolar disorder can result in serious problems that affect every area of your life, such as: Problems related to drug and alcohol use Suicide or suicide attempts Legal or financial problems Damaged ...

  8. Hoarding disorder

    Science.gov (United States)

    ... a reminder of happier times or representing beloved people or pets They feel safer when surrounded by the things ... that are part of hoarding disorder. Hoarding animals People who hoard animals may collect dozens or even hundreds of pets. Animals may be confined inside or outside. Because ...

  9. Anorectal Disorders

    Science.gov (United States)

    Rao, Satish S. C.; Bharucha, Adil E.; Chiarioni, Giuseppe; Felt-Bersma, Richelle; Knowles, Charles; Malcolm, Allison; Wald, Arnold

    2016-01-01

    This report defines criteria and reviews the epidemiology, pathophysiology, and management of the following common anorectal disorders: fecal incontinence (FI), functional anorectal pain, and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals, and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into 3 subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome and unspecified anorectal pain, the pain lasts more than 30 minutes, but in levator ani syndrome there is puborectalis tenderness. Functional defecation disorders are defined by ≥2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with ≥2 features of impaired evacuation, that is, abnormal evacuation pattern on manometry, abnormal balloon expulsion test, or impaired rectal evacuation by imaging. It includes 2 subtypes: dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating levator ani syndrome and defecatory disorders. PMID:27144630

  10. Depressive Disorders

    Science.gov (United States)

    Brown, Jacqueline A.; Russell, Samantha; Rasor, Kaitlin

    2017-01-01

    Depression is among the most common mental disorders in the United States. Its diagnosis is often related to impairment of functioning across several domains, including how an individual thinks, feels, and participates in daily activities. Although depression has a relatively high prevalence among adults, the rate is alarmingly higher among…

  11. Eating disorders

    Directory of Open Access Journals (Sweden)

    Kontić Olga

    2012-01-01

    Full Text Available Eating disorders are considered chronic diseases of civilization. The most studied and well known are anorexia and bulimia nervosa. Anorexia is considered one of the most common psychiatric problems of girls in puberty and adolescence. Due to high mortality and morbidity as well as the increasing expansion of these diseases, it is clear why the amount of research on these diseases is growing worldwide. Eating disorders lead to numerous medical complications, mostly due to late diagnosis. The main characteristic of these diseases is changed behavior in the nutrition, either as an intentional restriction of food, i.e. extreme dieting, or overeating, i.e. binge eating. Extreme dieting, skipping meals, self-induced vomiting, excessive exercise, and misuse of laxatives and diuretics for the purpose of maintaining or reducing body weight are characteristic forms of compensatory behavior of patients with eating disorder. The most appropriate course of treatment is determined by evaluating the patient’s health condition, associated with behavior and eating habits, the experience of one’s own body, character traits of personality, and consequently the development and functioning of the individual. The final treatment plan is individual. Eating disorders are a growing medical problem even in this part of the world. Prevention should be planned in cooperation with different sectors so as to stop the epidemic of these diseases.

  12. Balance Disorders

    Science.gov (United States)

    ... vertigo. If you have additional problems with motor control, such as weakness, slowness, tremor, or rigidity, you can lose your ability to recover properly from imbalance. This raises the risk of falling and injury. What are some types of balance disorders? There are more than a dozen different ...

  13. Vascular Disorders

    Science.gov (United States)

    ... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Vascular Disorders Email to a friend * required fields ...

  14. Autism and Related Disorders

    Science.gov (United States)

    McPartland, James; Volkmar, Fred R.

    2012-01-01

    The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

  15. Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay

    Directory of Open Access Journals (Sweden)

    Zavolan Mihaela

    2010-10-01

    Full Text Available Abstract Background In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate. Results In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs. Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1's role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3' UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms. Conclusions Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels.

  16. Bipolar Disorder and Obsessive Compulsive Disorder Comorbidity

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2014-08-01

    Full Text Available The comorbidity of bipolar disorder and anxiety disorders is a well known concept. Obsessive-compulsive disorder is the most commonly seen comorbid anxiety disorder in bipolar patients. Some genetic variants, neurotransmitters especially serotonergic systems and second-messenger systems are thought to be responsible for its etiology. Bipolar disorder alters the clinical aspects of obsessive compulsive disorder and is associated with poorer outcome. The determination of comorbidity between bipolar disorder and obsessive compulsive disorder is quite important for appropriate clinical management and treatment. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 429-437

  17. What Are Related Disorders?

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Contact Us Donate Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ...

  18. Panic Disorder among Adults

    Science.gov (United States)

    ... Disorder Among Adolescents Data Sources Share Panic Disorder Definition Panic Disorder is an anxiety disorder characterized by ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  19. Personality disorders

    DEFF Research Database (Denmark)

    Simonsen, Sebastian; Heinskou, Torben; Sørensen, Per

    2017-01-01

    BACKGROUND: In this naturalistic study, patients with personality disorders (N = 388) treated at Stolpegaard Psychotherapy Center, Mental Health Services, Capital Region of Denmark were allocated to two different kinds of treatment: a standardized treatment package with a preset number of treatment...... characteristics associated with clinicians' allocation of patients to the two different personality disorder services. METHODS: Patient characteristics across eight domains were collected in order to study whether there were systematic differences between patients allocated to the two different treatments....... Patient characteristics included measures of symptom severity, personality pathology, trauma and socio-demographic characteristics. Significance testing and binary regression analysis were applied to identify important predictors. RESULTS: Patient characteristics on fifteen variables differed...

  20. Disordered eating practices in gastrointestinal disorders.

    Science.gov (United States)

    Satherley, R; Howard, R; Higgs, S

    2015-01-01

    To systematically review evidence concerning disordered eating practices in dietary-controlled gastrointestinal conditions. Three key questions were examined: a) are disordered eating practices a feature of GI disorders?; b) what abnormal eating practices are present in those with GI disorders?; and c) what factors are associated with the presence of disordered eating in those with GI disorders? By exploring these questions, we aim to develop a conceptual model of disordered eating development in GI disease. Five key databases, Web of Science with Conference Proceedings (1900-2014) and MEDLINE (1950-2014), PubMed, PsycINFO (1967-2014) and Google Scholar, were searched for papers relating to disordered eating practices in those with GI disorders. All papers were quality assessed before being included in the review. Nine papers were included in the review. The majority of papers reported that the prevalence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls. Disordered eating patterns in dietary-controlled GI disorders may be associated with both anxiety and GI symptoms. Evidence concerning the correlates of disordered eating was limited. The presence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls, but the direction of the relationship is not clear. Implications for further research are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Social Anxiety Disorder and Mood Disorders Comorbidity

    Directory of Open Access Journals (Sweden)

    Zerrin Binbay

    2012-03-01

    Full Text Available Social Anxiety Disorder is a common disorder leading functional impairment. The comorbidity between mood disorders with social anxiety disorder is relatively common. This comorbidity impacts the clinical severity, resistance and functionality of patients. The systematic evaluation of the comorbidity in both patient groups should not be ignored and be carefully conducted. In general, social anxiety disorder starts at an earlier age than mood disorders and is reported to be predictor for subsequent major depression. The absence of comorbidity in patients with social anxiety disorder is a predictor of good response to treatment. In bipolar disorder patients with comorbid social anxiety disorder, there is an increased level of general psychopathology. Besides, they have poor outcome and increased risk of suicide. In this article, comorbidity between these two disorders has been evaluated in detail.

  2. Imprinting disorders

    DEFF Research Database (Denmark)

    Eggermann, Thomas; Perez de Nanclares, Guiomar; Maher, Eamonn R

    2015-01-01

    Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA...... sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical...

  3. Treatment of anxiety disorders

    OpenAIRE

    Bandelow, Borwin; Michaelis, Sophie; Wedekind, Dirk

    2017-01-01

    Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses...

  4. Conduct disorders.

    Science.gov (United States)

    Buitelaar, Jan K; Smeets, Kirsten C; Herpers, Pierre; Scheepers, Floor; Glennon, Jeffrey; Rommelse, Nanda N J

    2013-02-01

    Conduct disorder (CD) is a frequently occurring psychiatric disorder characterized by a persistent pattern of aggressive and non-aggressive rule breaking antisocial behaviours that lead to considerable burden for the patients themselves, their family and society. This review paper updates diagnostic and therapeutic approaches to CD in the light of the forthcoming DSM-5 definition. The diagnostic criteria for CD will remain unchanged in DSM-5, but the introduction of a specifier of CD with a callous-unemotional (CU) presentation is new. Linked to this, we discuss the pros and cons of various other ways to subtype aggression/CD symptoms. Existing guidelines for CD are, with few exceptions, already of a relatively older date and emphasize that clinical assessment should be systematic and comprehensive and based on a multi-informant approach. Non-medical psychosocial interventions are recommended as the first option for the treatment of CD. There is a role for medication in the treatment of comorbid syndromes and/or in case of insufficient response to psychosocial interventions and severe and dangerous aggressive and violent behaviours.

  5. Reducible and nonsensical uses of game theory

    NARCIS (Netherlands)

    de Bruin, B.P.

    The mathematical tools of game theory are frequently used in the social sciences and economic consultancy. But how do they explain social phenomena and support prescriptive judgments? And is the use of game theory really necessary? I analyze the logical form of explanatory and prescriptive game

  6. Sense and nonsense about the impact factor

    NARCIS (Netherlands)

    Opthof, T.

    1997-01-01

    The impact factor is based on citations of papers published by a scientific journal. It has been published since 1961 by the Institute for Scientific Information. It may be regarded as an estimate of the citation rate of a journal's papers, and the higher its value, the higher the scientific esteem

  7. Oxytocin and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Gokce Nur Say

    2016-06-01

    Full Text Available Oxytocin is a neuropeptide that plays critical role in mother-infant bonding, pair bonding and prosocial behaviors. Several neuropsychiatric disorders such as autism, schizophrenia, affective disorders, anxiety disorders, attention deficit/hyperactivity disorder, alcohol/substance addiction, aggression, suicide, eating disorders and personality disorders show abnormalities of oxytocin system. These findings have given rise to the studies searching therapeutic use of oxytocin for psychi-atric disorders. The studies of oxytocin interventions in psychiatric disorders yielded potentially promising findings. This paper reviews the role of oxytocin in emotions, behavior and its effects in psychiatric disorders. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 102-113

  8. Sleep Disorders in Childhood Neurogenetic Disorders

    Directory of Open Access Journals (Sweden)

    Laura Beth Mann Dosier

    2017-09-01

    Full Text Available Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.

  9. Coffin-Siris syndrome is a SWI/SNF complex disorder.

    Science.gov (United States)

    Tsurusaki, Y; Okamoto, N; Ohashi, H; Mizuno, S; Matsumoto, N; Makita, Y; Fukuda, M; Isidor, B; Perrier, J; Aggarwal, S; Dalal, A B; Al-Kindy, A; Liebelt, J; Mowat, D; Nakashima, M; Saitsu, H; Miyake, N; Matsumoto, N

    2014-06-01

    Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Posttraumatic Stress Disorder

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Posttraumatic Stress Disorder (PTSD) KidsHealth / For Parents / Posttraumatic Stress Disorder ( ... My Child? Looking Ahead Print What Is Posttraumatic Stress Disorder (PTSD)? Someone who is the victim of ( ...

  11. Pterins and affective disorders

    NARCIS (Netherlands)

    R. Hoekstra (Rocco)

    2007-01-01

    textabstractThe pathophysiology of affective disorders is largely unknown. In patients with various affective disorders the activity of pterins and related amino acids were investigated before and after clinical treatment. In particular the bipolar affective disorder could be

  12. Paediatric Anxiety Disorders

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2017-07-01

    Full Text Available Anxiety disorders are highly prevalent among children and are associated with serious morbidity. Lifetime prevalence of paediatric anxiety disorders is about fifteen percent. Social phobia, generalized anxiety disorder and separation anxiety disorder are included in the triad of paediatric anxiety disorders. Specific phobia, obsessive compulsive disorder and post-traumatic stress disorder are also commonly seen in children. Overprotection by parents, parental death or separation, female sex, low educational status, family history of anxiety disorder, financial stress in family and adverse childhood experiences are risk factors for the development of anxiety disorders. If not diagnosed and managed at the earliest, paediatric anxiety disorders can cause life threatening problems in the future. Hence early and scientific management of anxiety disorders is essential. Cognitive behavioural therapy is the effective evidence based treatment for paediatric anxiety disorders.

  13. Social anxiety disorder

    Science.gov (United States)

    Phobia - social; Anxiety disorder - social; Social phobia; SAD - social anxiety disorder ... People with social anxiety disorder fear and avoid situations in which they may be judged by others. It may begin in ...

  14. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  15. Pituitary Gland Disorders Overview

    Science.gov (United States)

    ... Peer Support Resources Diseases and Conditions Adrenal Disorders Osteoporosis and Bone Health Children and Teen Health Diabetes Heart Health Men's Health Rare Diseases Pituitary Disorders Thyroid Disorders Transgender Health Obesity and Weight Management Women's Health You and Your ...

  16. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  17. Eating disorder symptoms in affective disorder.

    OpenAIRE

    Wold, P N

    1991-01-01

    Patients with Major Affective Disorder (MAD), Secondary Depression, Panic Disorder, and bulimia with and without MAD, were given the Eating Disorder Inventory, the Beck Depression Inventory, and the General Behavior Inventory at presentation. It was found that patients with MAD have a triad of eating disorder symptoms: a disturbance in interoceptive awareness, the sense of ineffectiveness, and a tendency toward bulimia. The data supported the concept that the sense of ineffectiveness is secon...

  18. ACE: Health - Neurodevelopmental Disorders

    Science.gov (United States)

    Information about children reported to have ever been diagnosed with four different neurodevelopmental disorders: attention-deficit/hyperactivity disorder (ADHD), learning disabilities, autism, and intellectual disability.

  19. Autism Spectrum Disorders (Pervasive Developmental Disorders)

    Science.gov (United States)

    Strock, Margaret

    2007-01-01

    This booklet focuses on classic autism, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome, with brief descriptions of Rett syndrome and childhood disintegrative disorder. The booklet describes possible indicators of autism spectrum disorders (ASD), their diagnosis, available aids, treatment options, adults…

  20. Comorbidity of bipolar disorder and eating disorders.

    Science.gov (United States)

    Álvarez Ruiz, Eva M; Gutiérrez-Rojas, Luis

    2015-01-01

    The comorbidity of bipolar disorder and eating disorders has not been studied in depth. In addition, clinical implications involved in the appearance of both disorders are very important. A systematic literature review of MEDLINE published up to September 2013 was performed, analyzing all the articles that studied the comorbidity of both conditions (bipolar disorder and eating disorders) and others research that studied the efficacy of pharmacological treatment and psychotherapy to improve these illnesses. In this review we found a high comorbidity of bipolar disorder and eating disorders, especially of bulimia nervosa and binge eating disorder. Studies show that lithium and topiramate are 2 of the more effective pharmacological agents in the treatment of both disorders. There are a lot of studies that show evidence of comorbidity of bipolar disorder and eating disorders. However, further research is needed on assessment and treatment when these conditions co-exist, as well as study into the biopsychological aspects to determine the comorbid aetiology. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  1. Vaginal disorders.

    Science.gov (United States)

    Soderberg, S F

    1986-05-01

    Chronic vaginitis is the most common vaginal disorder. Dogs with vaginitis show no signs of systemic illness but often lick at the vulva and have purulent or hemorrhagic vaginal discharges. Vaginitis is most commonly secondary to a noninfectious inciting factor such as congenital vaginal anomalies, clitoral hypertrophy, foreign bodies, trauma to the vaginal mucosa, or vaginal tumors. Inspection of the caudal vagina and vestibule both visually and digitally will often reveal the source of vaginal irritation. Vaginal cytology is used to establish the stage of the estrous cycle as well as distinguish uterine from vaginal sources of discharge. Vaginal cultures are used to establish the predominant offending organism associated with vaginal discharges and may be used as a guide for selection of a therapeutic agent. Vaginitis is best managed by removing the inciting cause and treating the area locally with antiseptic douches. Congenital malformations at the vestibulovaginal or vestibulovulvar junction may prevent normal intromission. Affected bitches may be reluctant to breed naturally because of pain. Such defects are detected best by digital examination. Congenital vaginal defects may be corrected by digital or surgical means. Prolapse of tissue through the lips of the vulva may be caused by clitoral hypertrophy, vaginal hyperplasia, or vaginal tumors. Enlargement of clitoral tissue is the result of endogenous or exogenous sources of androgens. Treatment of this condition includes removal of the androgen source and/or surgical removal of clitoral tissue. Vaginal hyperplasia is detected during proestrus or estrus of young bitches. Hyperplastic tissue will regress during diestrus. Tissue that is excessively traumatized and/or prolapse of the entire vaginal circumference may be removed surgically. Ovariohysterectomy may be used to prevent recurrence. Vaginal tumors are detected most often in older intact bitches. Such tumors are generally of smooth muscle or fibrous

  2. Conduct Disorder and Comorbidity.

    Science.gov (United States)

    Stahl, Nicole D.; Clarizio, Harvey F.

    1999-01-01

    Provides critical examination of research published during past ten years addressing Conduct Disorder (CD), Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder (ODD), and internalizing disorders. Concludes comorbidity varies with age, gender, informant, diagnostic criteria, and nature of the sample. Implications of comorbidity…

  3. Intermittent Explosive Disorder

    Directory of Open Access Journals (Sweden)

    Lut Tamam

    2011-09-01

    Full Text Available Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etiological studies displayed the role of both psychosocial factors like childhood traumas and biological factors like dysfunctional neurotransmitter systems and genetics. In differential diagnosis of the disorder, disorders involving agression as a symptom such as alcohol and drug intoxication, antisocial and borderline personality disorders, personality changes due to general medical conditions and behavioral disorder should be considered. A combination of pharmacological and psychotherapeutic approaches are suggested in the treatment of the disorder. This article briefly reviews the historical background, diagnostic criteria, epidemiology, etiology and treatment of intermittent explosive disorder.

  4. Characterization of RACK7 as a Novel Factor Involved in BRCA1 Mutation Mediated Breast Cancer

    Science.gov (United States)

    2012-10-01

    which may associate with methylated histones; a Bromodomain that can bind acetyl-lysine; a Pro- Trp - Trp -Pro (PWWP) 4 domain , which also binds...Institute for Biological Studies La Jolla, CA 92037 Though BRCA1 has been shown to play a role in DNA end resection, likely critical in the cell’s...mating yielded no pups, likely a result of the age of the floxed p53 mice upon receipt from a collaborating laboratory. Due to the lack of

  5. DNA mutations mediate microevolution between host-adapted forms of the pathogenic fungus Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Denise A Magditch

    Full Text Available The disease cryptococcosis, caused by the fungus Cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. One explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. However, co-incubation of C. neoformans with amoeba can cause a "switch" from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence in mammalian models of cryptococcosis. Like other human pathogenic fungi, C. neoformans is capable of microevolutionary changes that influence the biology of the organism and outcome of the host-pathogen interaction. A yeast-pseudohyphal phenotypic switch also happens under in vitro conditions. Here, we demonstrate that this morphological switch, rather than being under epigenetic control, is controlled by DNA mutation since all pseudohyphal strains bear mutations within genes encoding components of the RAM pathway. High rates of isolation of pseudohyphal strains can be explained by the physical size of RAM pathway genes and a hypermutator phenotype of the strain used in phenotypic switching studies. Reversion to wild type yeast morphology in vitro or within a mammalian host can occur through different mechanisms, with one being counter-acting mutations. Infection of mice with RAM mutants reveals several outcomes: clearance of the infection, asymptomatic maintenance of the strains, or reversion to wild type forms and progression of disease. These findings demonstrate a key role of mutation events in microevolution to modulate the ability of a fungal pathogen to cause disease.

  6. Adult onset tic disorders

    OpenAIRE

    Chouinard, S.; Ford, B.

    2000-01-01

    BACKGROUND—Tic disorders presenting during adulthood have infrequently been described in the medical literature. Most reports depict adult onset secondary tic disorders caused by trauma, encephalitis, and other acquired conditions. Only rare reports describe idiopathic adult onset tic disorders, and most of these cases represent recurrent childhood tic disorders.
OBJECTIVE—To describe a large series of patients with tic disorders presenting during adulthood, to compare cl...

  7. BIPOLAR DISORDER: A REVIEW

    OpenAIRE

    Pathan Dilnawaz N; Ziyaurrahaman A.R; Bhise K.S.

    2010-01-01

    Bipolar disorder (BD) is a severe psychiatric disorder that results in poor global functioning, reduced quality of life and high relapse rates. Research finds that many adults with bipolar disorder identify the onset of symptoms in childhood and adolescence, indicating the importance of early accurate diagnosis and treatment. Accurate diagnosis of mood disorders is critical for treatment to be effective. Distinguishing between major depression and bipolar disorders, especially the depressed p...

  8. Anxiety Disorders and the Family: How families affect psychiatric disorders

    OpenAIRE

    Hunsley, John

    1991-01-01

    Family functioning and anxiety disorders, the most prevalent forms of psychiatric disorder, influence one another. The empirical literature on family studies of anxiety disorder (ie, aggregration of disorders within families), on parent-child relationships and anxiety disorders, and on marriage and anxiety disorders is reviewed. Finally, the challenges for patients and their families of post-traumatic stress disorder are discussed.

  9. Comorbidity bipolar disorder and personality disorders.

    Science.gov (United States)

    Latalova, Klara; Prasko, Jan; Kamaradova, Dana; Sedlackova, Jana; Ociskova, Marie

    2013-01-01

    Outcome in bipolar patients can be affected by comorbidity of other psychiatric disorders. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. We have much information about treating patients with uncomplicated bipolar disorder (BD) but much less knowledge about possibilities for patients with the comorbidity of BD and personality disorder. We conducted a series of literature searches using, as key words or as items in indexed fields, bipolar disorder and personality disorder or personality traits. Articles were obtained by searching MEDLINE from 1970 to 2012. In addition, we used other papers cited in articles from these searches, or cited in articles used in our own work. Tests of personality traits indicated that euthymic bipolar patients have higher scores on harm avoidance, reward dependence, and novelty seeking than controls. Elevation of novelty seeking in bipolar patients is associated with substance abuse comorbidity. Comorbidity with personality disorders in BD patients is associated with a more difficult course of illness (such as longer episodes, shorter time euthymic, and earlier age at onset) and an increase in comorbid substance abuse, suicidality and aggression. These problems are particularly pronounced in comorbidity with borderline personality disorder. Comorbidity with antisocial personality disorder elicits a similar spectrum of difficulties; some of the antisocial behavior exhibited by patients with this comorbidity is mediated by increased impulsivity.

  10. Binge Eating Disorder

    Directory of Open Access Journals (Sweden)

    Senol Turan

    2015-12-01

    Full Text Available Binge Eating Disorder, characterized by frequent and persistent overeating episodes that are accompanied by feeling of loss of control over eating without regular compensatory behaviors and was identified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as a new eating disorder category. Binge Eating Disorder is the most common eating disorder among adults. Binge Eating Disorder is associated with significant morbidity, including medical complications related to obesity, eating disorder psychopathology, psychiatric comorbidity; reduced quality of life, and impaired social functioning. Current treatments of Binge Eating Disorder include pharmacotherapy, psychotherapy and bariatric surgery. In this review, the definition, epidemiology, etiology, clinical features, and also mainly treatment of Binge Eating Disorder are discussed.

  11. Reviews Equipment: Chameleon Nano Flakes Book: Requiem for a Species Equipment: Laser Sound System Equipment: EasySense VISION Equipment: UV Flash Kit Book: The Demon-Haunted World Book: Nonsense on Stilts Book: How to Think about Weird Things Web Watch

    Science.gov (United States)

    2011-03-01

    WE RECOMMEND Requiem for a Species This book delivers a sober message about climate change Laser Sound System Sound kit is useful for laser demonstrations EasySense VISION Data Harvest produces another easy-to-use data logger UV Flash Kit Useful equipment captures shadows on film The Demon-Haunted World World-famous astronomer attacks pseudoscience in this book Nonsense on Stilts A thought-provoking analysis of hard and soft sciences How to Think about Weird Things This book explores the credibility of astrologers and their ilk WORTH A LOOK Chameleon Nano Flakes Product lacks good instructions and guidelines WEB WATCH Amateur scientists help out researchers with a variety of online projects

  12. Bipolar disorder in adolescence.

    Science.gov (United States)

    DeFilippis, Melissa; Wagner, Karen Dineen

    2013-08-01

    Bipolar disorder is a serious psychiatric condition that may have onset in childhood. It is important for physicians to recognize the symptoms of bipolar disorder in children and adolescents in order to accurately diagnose this illness early in its course. Evidence regarding the efficacy of various treatments is necessary to guide the management of bipolar disorder in youth. For example, several medications commonly used for adults with bipolar disorder have not shown efficacy for children and adolescents with bipolar disorder. This article reviews the prevalence, diagnosis, course, and treatment of bipolar disorder in children and adolescents and provides physicians with information that will aid in diagnosis and treatment.

  13. Narrative Ability of Children With Speech Sound Disorders and the Prediction of Later Literacy Skills

    Science.gov (United States)

    Wellman, Rachel L.; Lewis, Barbara A.; Freebairn, Lisa A.; Avrich, Allison A.; Hansen, Amy J.; Stein, Catherine M.

    2012-01-01

    Purpose The main purpose of this study was to examine how children with isolated speech sound disorders (SSDs; n = 20), children with combined SSDs and language impairment (LI; n = 20), and typically developing children (n = 20), ages 3;3 (years;months) to 6;6, differ in narrative ability. The second purpose was to determine if early narrative ability predicts school-age (8–12 years) literacy skills. Method This study employed a longitudinal cohort design. The children completed a narrative retelling task before their formal literacy instruction began. The narratives were analyzed and compared for group differences. Performance on these early narratives was then used to predict the children’s reading decoding, reading comprehension, and written language ability at school age. Results Significant group differences were found in children’s (a) ability to answer questions about the story, (b) use of story grammars, and (c) number of correct and irrelevant utterances. Regression analysis demonstrated that measures of story structure and accuracy were the best predictors of the decoding of real words, reading comprehension, and written language. Measures of syntax and lexical diversity were the best predictors of the decoding of nonsense words. Conclusion Combined SSDs and LI, and not isolated SSDs, impact a child’s narrative abilities. Narrative retelling is a useful task for predicting which children may be at risk for later literacy problems. PMID:21969531

  14. CDKL5 variants: Improving our understanding of a rare neurologic disorder.

    Science.gov (United States)

    Hector, Ralph D; Kalscheuer, Vera M; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E S; Cobb, Stuart R

    2017-12-01

    To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain.

  15. [Obsessive-compulsive disorder. A hidden disorder].

    Science.gov (United States)

    Haraldsson, Magnús

    2015-02-01

    Obsessive-compulsive disorder is a common and often chronic psychiatric illness that significantly interferes with the patient´s functioning and quality of life. The disorder is characterized by excessive intrusive and inappropriate anxiety evoking thoughts as well as time consuming compulsions that cause significant impairment and distress. The symptoms are often accompanied by shame and guilt and the knowledge of the general public and professional community about the disorder is limited. Hence it is frequently misdiagnosed or diagnosed late. There are indications that the disorder is hereditary and that neurobiological processes are involved in its pathophysiology. Several psychological theories about the causes of obsessive-compulsive disorder are supported by empirical evidence. Evidence based treatment is either with serotoninergic medications or cognitive behavioral therapy, particularly a form of behavioral therapy called exposure response prevention. Better treatment options are needed because almost a third of people with obsessive-compulsive disorder respond inadequatly to treatment. In this review article two cases of obsessive-compulsive disorder are presented. The former case is a young man with typical symptoms that respond well to treatment and the latter is a middle aged lady with severe treatment resistant symptoms. She underwent stereotactic implantation of electrodes and received deep brain stimulation, which is an experimental treatment for severe obsessive-compulsive disorder that does not respond to any conventional treatment. Landspitali University Hospital, Division of Psychiatry. Faculty of Medicine, University of Iceland.

  16. Autism spectrum disorder - Asperger syndrome

    Science.gov (United States)

    ... part of the larger developmental disorder category of autism spectrum disorder . ... American Psychiatric Association. Autism spectrum disorder. ... VA: American Psychiatric Publishing: 2013;50-59. Raviola GJ, ...

  17. Tic Disorder and ADHD

    OpenAIRE

    J Gordon Millichap

    2001-01-01

    The behavioral and neuropsychological characteristics of tic disorder, with or without attention-deficit hyperactivity disorder (ADHD), were examined in 78 children followed at Seoul National University College of Medicine, Korea.

  18. Stereotypic movement disorder

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001548.htm Stereotypic movement disorder To use the sharing features on this page, please enable JavaScript. Stereotypic movement disorder is a condition in which a person makes ...

  19. Co-Occurring Disorders

    Science.gov (United States)

    ... the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring Disorders and ... 500 Montgomery Street, Suite 820 Alexandria, VA 22314 Phone (703) 684.7722 Toll Free (800) 969.6642 ...

  20. Sleep and Eating Disorders.

    Science.gov (United States)

    Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

    2016-10-01

    Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

  1. Genetic Brain Disorders

    Science.gov (United States)

    A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

  2. Speech and Communication Disorders

    Science.gov (United States)

    ... to being completely unable to speak or understand speech. Causes include Hearing disorders and deafness Voice problems, ... or those caused by cleft lip or palate Speech problems like stuttering Developmental disabilities Learning disorders Autism ...

  3. Eye Movement Disorders

    Science.gov (United States)

    ... work properly. There are many kinds of eye movement disorders. Two common ones are Strabismus - a disorder ... in "crossed eyes" or "walleye." Nystagmus - fast, uncontrollable movements of the eyes, sometimes called "dancing eyes" Some ...

  4. Overview of Movement Disorders

    Science.gov (United States)

    ... of Delirium Additional Content Medical News Overview of Movement Disorders By Hector A. Gonzalez-Usigli, MD, Professor ... Neurology, HE UMAE Centro Médico Nacional de Occidente; Movement Disorders Clinic, Neurology at IMSS Alberto Espay, MD, ...

  5. Autism Spectrum Disorder

    Science.gov (United States)

    ... Caregiver Education » Fact Sheets Autism Spectrum Disorder Fact Sheet What is autism spectrum disorder? What are some ... of mutations in individual genes but rather spontaneous coding mutations across many genes. De novo mutations may ...

  6. What Are Reading Disorders?

    Science.gov (United States)

    ... and language-based learning disabilities are commonly called dyslexia . These disorders are present from a young age ... information about these problems. Types of Reading Disorders Dyslexia is a brain-based type of learning disability ...

  7. Males and Eating Disorders

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Males and Eating Disorders Past Issues / Spring 2008 Table of Contents For ... this page please turn Javascript on. Photo: PhotoDisc Eating disorders primarily affect girls and women, but boys and ...

  8. Neuroimaging of neurotic disorders

    International Nuclear Information System (INIS)

    Okubo, Yoshiro; Yahata, Noriaki

    2006-01-01

    Neuroimaging has been involved in recent biological approaches with evidence for neurotic disorders in place of diagnostic criteria on Freud theory hitherto. This review describes the present states of brain imaging in those disorders. Emotion has such three bases for environmental stimuli as recognition/evaluation of causable factors, manifestation, and its control, each of which occurs in various different regions connected by neuro-net work in the brain. The disorders are regarded as abnormality of the circuit that can be imaged. Documented and discussed are the actual regions imaged by MRI and PET in panic disorder, social phobia, phobias to specified things, posttraumatic stress disorder and obsessive-compulsive disorder. The approach is thought important for elucidating not only the pathogenesis of the disorders but also the human emotional functions and mechanism of the mind, which may lead to a better treatment of the disorders in future. (T.I)

  9. Diagnosing Tic Disorders

    Science.gov (United States)

    ... Submit" /> Information For… Media Policy Makers Diagnosing Tic Disorders Language: English (US) Español (Spanish) Recommend on ... or postviral encephalitis). Persistent (Chronic) Motor or Vocal Tic Disorder To be diagnosed with a persistent tic ...

  10. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  11. Alcohol use disorder

    Science.gov (United States)

    ... have problems with alcohol if you: Are a young adult under peer pressure Have depression, bipolar disorder , anxiety disorders , or schizophrenia Can easily obtain alcohol Have low self-esteem Have problems with relationships Live a stressful lifestyle ...

  12. Language disorder - children

    Science.gov (United States)

    ... disorders are rarely caused by a lack of intelligence. Language disorders are different than delayed language. With ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  13. Bipolar disorder: an overview

    African Journals Online (AJOL)

    manic-depressive disorder, is a chronic disorder characterised by abnormal mood ... of onset, family history, atypical features and mixed symptoms. Screening tools .... has been associated with mood irritability, anxiety, mania and psychosis.

  14. Betaxolol in anxiety disorders.

    Science.gov (United States)

    Swartz, C M

    1998-03-01

    Betaxolol, a long-acting beta-adrenergic blocker that enters the central nervous system, was examined for therapeutic effects on the persistent anxiety of anxiety disorders. Prior studies of beta-blockers examined only agents that were short-acting or did not enter the brain. Betaxolol was administered to 31 patients in open trials. Of 13 outpatients, 11 had generalized anxiety disorder (GAD) and 2 had adjustment disorder with anxiety. Five with GAD had concurrent panic disorder. Of 18 inpatients, 16 had GAD and 2 had adjustment disorder with anxiety. Betaxolol doses were increased until the patient responded or declined further dosage. Severity was rated on a 4-point global scale. Before betaxolol, all were moderately or severely ill. In all patients with panic disorder panic attacks stopped within 2 days (pAnxiety decreased to no more than marginally ill in 85% of outpatients (panxiety and obsessive-compulsive personality disorder. Preliminary observations in posttraumatic stress disorder are similar.

  15. Heart Diseases and Disorders

    Science.gov (United States)

    ... Resources Heart Diseases & Disorders Back to Patient Resources Heart Diseases & Disorders Millions of people experience irregular or abnormal ... harmless and happen in healthy people free of heart disease. However, some abnormal heart rhythms can be serious ...

  16. Body Dysmorphic Disorder

    Science.gov (United States)

    ... compulsive disorder. Environment. Your environment, life experiences and culture may contribute to body dysmorphic disorder, especially if they involve negative social evaluations about your body or self-image, or even childhood neglect or abuse. Risk factors ...

  17. Reproductive Disorders in Snakes.

    Science.gov (United States)

    Di Girolamo, Nicola; Selleri, Paolo

    2017-05-01

    Reproduction of snakes is one of the challenging aspects of herpetology medicine. Due to the complexity of reproduction, several disorders may present before, during, or after this process. This article describes the physical examination, and radiographic, ultrasonographic, and endoscopic findings associated with reproductive disorders in snakes. Surgical techniques used to resolve reproductive disorders in snakes are described. Finally, common reproductive disorders in snakes are individually discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Sleep and anxiety disorders

    OpenAIRE

    Staner, Luc

    2003-01-01

    Sleep disturbances-particularly insomnia - are highly prevalent in anxiety disorders and complaints such as insomnia or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and the locus ceruleus-a...

  19. Generalised anxiety disorder

    OpenAIRE

    Gale, Christopher K; Millichamp, Jane

    2011-01-01

    Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, ...

  20. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

  1. Common anorectal disorders.

    Science.gov (United States)

    Foxx-Orenstein, Amy E; Umar, Sarah B; Crowell, Michael D

    2014-05-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management.

  2. Sexual Desire Disorders

    OpenAIRE

    Montgomery, Keith A.

    2008-01-01

    Hypoactive sexual desire disorder (HSDD) and sexual aversion disorder (SAD) are an under-diagnosed group of disorders that affect men and women. Despite their prevalence, these two disorders are often not addressed by healthcare providers and patients due their private and awkward nature. As physicians, we need to move beyond our own unease in order to adequately address our patients’ sexual problems and implement appropriate treatment. Using the Sexual Response Cycle as the model of the phys...

  3. Functional esophageal disorders

    OpenAIRE

    Clouse, R; Richter, J; Heading, R; Janssens, J; Wilson, J

    1999-01-01

    The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or p...

  4. Sequencing of sporadic Attention-Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder.

    Science.gov (United States)

    Kim, Daniel Seung; Burt, Amber A; Ranchalis, Jane E; Wilmot, Beth; Smith, Joshua D; Patterson, Karynne E; Coe, Bradley P; Li, Yatong K; Bamshad, Michael J; Nikolas, Molly; Eichler, Evan E; Swanson, James M; Nigg, Joel T; Nickerson, Deborah A; Jarvik, Gail P

    2017-06-01

    Attention-Deficit Hyperactivity Disorder (ADHD) has high heritability; however, studies of common variation account for ADHD variance. Using data from affected participants without a family history of ADHD, we sought to identify de novo variants that could account for sporadic ADHD. Considering a total of 128 families, two analyses were conducted in parallel: first, in 11 unaffected parent/affected proband trios (or quads with the addition of an unaffected sibling) we completed exome sequencing. Six de novo missense variants at highly conserved bases were identified and validated from four of the 11 families: the brain-expressed genes TBC1D9, DAGLA, QARS, CSMD2, TRPM2, and WDR83. Separately, in 117 unrelated probands with sporadic ADHD, we sequenced a panel of 26 genes implicated in intellectual disability (ID) and autism spectrum disorder (ASD) to evaluate whether variation in ASD/ID-associated genes were also present in participants with ADHD. Only one putative deleterious variant (Gln600STOP) in CHD1L was identified; this was found in a single proband. Notably, no other nonsense, splice, frameshift, or highly conserved missense variants in the 26 gene panel were identified and validated. These data suggest that de novo variant analysis in families with independently adjudicated sporadic ADHD diagnosis can identify novel genes implicated in ADHD pathogenesis. Moreover, that only one of the 128 cases (0.8%, 11 exome, and 117 MIP sequenced participants) had putative deleterious variants within our data in 26 genes related to ID and ASD suggests significant independence in the genetic pathogenesis of ADHD as compared to ASD and ID phenotypes. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Seizure Disorders in Pregnancy

    Science.gov (United States)

    ... If I have a seizure disorder, can it cause problems during pregnancy? • What risks are associated with having a seizure ... If I have a seizure disorder, can it cause problems during pregnancy? Seizure disorders can affect pregnancy in several ways: • ...

  6. Mood Disorders - Multiple Languages

    Science.gov (United States)

    ... Expand Section Mood Disorders: MedlinePlus Health Topic - English Trastornos del estado de ánimo: Tema de salud de MedlinePlus - español (Spanish) National Library of Medicine Bipolar Disorder (An Introduction) - English PDF Bipolar Disorder (An ...

  7. Separation anxiety disorder

    NARCIS (Netherlands)

    Nauta, M.H.; Emmelkamp, P.M.G.; Sturmey, P.; Hersen, M.

    2012-01-01

    Separation anxiety disorder (SAD) is the only anxiety disorder that is specific to childhood; however, SAD has hardly ever been addressed as a separate disorder in clinical trials investigating treatment outcome. So far, only parent training has been developed specifically for SAD. This particular

  8. Diagnosis of Mood Disorders.

    Science.gov (United States)

    Seligman, Linda; Moore, Bonita Marcus

    1995-01-01

    Provides an overview of mood disorders according to Diagnostic and Statistical Manual (fourth edition) criteria and other relevant information. Differential diagnosis is facilitated through discussion of differences and similarities among mental disorders, age and gender-related patterns of mood disorders, and useful diagnostic tools. (Author)

  9. Dissociative Identity Disorder

    Science.gov (United States)

    Schmidt, Tom

    2007-01-01

    Few psychological disorders in the Diagnostic Statistical Manual have generated as much controversy as Dissociative Identity Disorder (DID). For the past 35 years diagnoses of DID, previously referred to as Multiple Personality Disorder (MPD), have increased exponentially, causing various psychological researchers and clinicians to question the…

  10. Lipid Metabolism Disorders

    Science.gov (United States)

    ... using blood tests. If there is a family history of one of these disorders, parents can get genetic testing to see whether they carry the gene. Other genetic tests can tell whether the fetus has the disorder or carries the gene for the disorder. Enzyme replacement therapies can help with a few of ...

  11. Connective Tissue Disorders

    Science.gov (United States)

    ... of connective tissue. Over 200 disorders that impact connective tissue. There are different types: Genetic disorders, such as Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta Autoimmune disorders, such as lupus and scleroderma Cancers, like some types of soft tissue sarcoma Each ...

  12. Treatment of Schizoaffective Disorder

    OpenAIRE

    Cascade, Elisa; Kalali, Amir H.; Buckley, Peter

    2009-01-01

    In this article, we investigate the range of treatments prescribed for schizoaffective disorder. The data show that the majority of those treated, 87 percent, receive two or more pharmaceutical classes. From a therapeutic class perspective, 93 percent of schizoaffective disorder patients receive an antipsychotic, 48 percent receive a mood disorder treatment, and 42 percent receive an antidepressant. An expert commentary is also included.

  13. Dual Disorders in Adolescent Populations

    NARCIS (Netherlands)

    van West, D.; Vermeiren, R.R.J.M.

    2015-01-01

    Psychiatric comorbidity in adolescents who abuse substances is the rule rather than the exception, and common comorbidities include depression, anxiety disorder, bipolar disorder, conduct disorder, and Attention Deficit Hyperactivity Disorder (ADHD). Among adolescents, the presence of both mental

  14. Classification of movement disorders.

    Science.gov (United States)

    Fahn, Stanley

    2011-05-01

    The classification of movement disorders has evolved. Even the terminology has shifted, from an anatomical one of extrapyramidal disorders to a phenomenological one of movement disorders. The history of how this shift came about is described. The history of both the definitions and the classifications of the various neurologic conditions is then reviewed. First is a review of movement disorders as a group; then, the evolving classifications for 3 of them--parkinsonism, dystonia, and tremor--are covered in detail. Copyright © 2011 Movement Disorder Society.

  15. La Tourette's Disorder

    Directory of Open Access Journals (Sweden)

    Gabriel Fernando Oviedo Lugo

    2004-08-01

    Full Text Available Tourette Syndrome (TS is a complex neuropsychiatric disorder in which tic symptoms emerge prior to age of 18 and have, at least, a minimum duration of 12 months. This disorder produces distress and impairs normal functioning; it has a well-known chronic-waxing and waning course. TS has several comorbid conditions like obsessive-compulsive disorder, attention deficit-hyperactivity disorder, and learning disorders, among others. This article will review the epidemiologic, etiologic and phenomenological concepts of the disease and its therapeutic perspectives.

  16. Bipolar Disorder in Women

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2013-06-01

    Full Text Available The research on gender's role in bipolar disorders has drawn significant interest recently. The presentation and course of bipolar disorder differs between women and men. Women experience depressive episodes, dysphoric mood, mixed states, rapid cycling and seasonal patterns more often than men. Comorbidity, particularly thyroid disease, migraine, obesity, and anxiety disorders laso occur more frequently in women than men. On the other hand men with bipolar disorder are also more likely than women to have problems with drug or alcohol abuse. The pregnancy and postpartum period is a time of high risk for onset and recurrence of bipolar disorder in women.

  17. Chronobiology and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Yavuz Selvi

    2011-09-01

    Full Text Available Living organizms show cyclic rhythmicity in a variety of physiological, hormonal, behavioral, and psychological processes. Sleep-wake cycles, body temperature, hormone levels, mood and cognition display a circadian rhythm in humans. Delays, advances or desynchronizations of circadian rhythm are known to be strongly associated with mental illness especially mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the mood stabilizers, sleep deprivation and light treatment are employed to treat mood disorders by shifting circadian rhythm. This paper reviews the relationship between mood disorders and circadian rhythm, and describes treatment options by altering circadian rhythm.

  18. Generalised anxiety disorder

    Directory of Open Access Journals (Sweden)

    Bojana Avguštin Avčin

    2013-10-01

    Full Text Available Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, somatic illness, pain, fatigue and problems sleeping. The evaluation of prognosis is complicated by frequent comorbidity with other anxiety disorders and depression, which worsen the long-term outcome and accompanying burden of disability. The two main treatments for generalised anxiety disorder are medications and psychotherapy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors represent first-line psychopharmacologic treatment for generalised anxiety disorder. The most extensively studied psychotherapy for anxiety is cognitive behavioural therapy which has demonstrated efficacy throughout controlled studies.

  19. Genetics of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Kerner B

    2014-02-01

    Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are

  20. Comorbid personality disorders in subjects with panic disorder: which personality disorders increase clinical severity?

    OpenAIRE

    Mustafa Ozkan; Abdurrahman Altindag

    2003-01-01

    Personality disorders are common in subjects with panic disorder. Personality disorders have shown to affect the course of panic disorder. The purpose of this study was to examine which personality disorders effect clinical severity in subjects with panic disorder. This study included 122 adults (71 female, 41 male), who met DSM-IV criteria for panic disorder (with or without agoraphobia). Clinical assessment was conducted by using the Structured Clinical Interview for DSM-IV Axis I Disorders...

  1. [Rethink the panic disorder].

    Science.gov (United States)

    Amami, O; Aloulou, J; Siala, M; Aribi, L

    2010-04-01

    We propose some reflexions on the validity of the conceptualization of panic disorder, its nosographical place, and its clinical homogeneity, through the study of the frequency of some of its psychiatric comorbidities. To define a panic attack, DSM IV requires a number of symptoms which vary from four to 13. However, some patients suffer from panic attacks with less than four symptoms (paucisymptomatic attacks) and which fill the other criteria of panic disorder. These patients would have a biological vulnerability, familial antecedents, and a treatment response which are similar to those that fill the criteria of the panic attack according to the DSM. Some authors differentiate the panic disorder in several sub-groups, such as the panic disorder with cardiorespiratory symptoms, or vestibular symptoms, or cognitive symptoms. This division of the panic disorder in several sub-groups would have an interest in the knowledge of the etiopathogeny, the attacks' frequency, the disorder severity and the treatment response. Panic disorder with prevalent somatic expression includes crises without cognitive symptoms. This sub-type can be common in the medical context, especially in cardiology, but it is often ignored, at the price of loss of socio-professional adaptability, and a medical overconsumption. The relationship between panic disorder and agoraphobia appears to be the subject of controversies. According to the behavioral theory, phobic disorder is the primum movens of the sequence of appearance of the disorders. American psychiatry considers agoraphobia as a secondary response to the panic disorder, and pleads for a central role of panic attacks as an etiopathogenic factor in the development of agoraphobia. The distinction between panic disorder and generalized anxiety disorder can be difficult. This is due to the existence of paucisymptomatic panic attacks. Their paroxystic nature is difficult to distinguish from the fluctuations of the generalized anxiety disorder

  2. Paraneoplastic autoimmune movement disorders.

    Science.gov (United States)

    Lim, Thien Thien

    2017-11-01

    To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. [Gambling disorder in Japan].

    Science.gov (United States)

    Tanabe, Hitoshi

    2015-09-01

    Gambling disorder is a psychiatric disorder characterized by persistent and recurrent problematic gambling behavior, associated with impaired functioning, reduced quality of life, and frequent divorce and bankruptcy. Gambling disorder is reclassified in the category Substance-Related and Addictive Disorders in the DSM-5 because its clinical features closely resemble those of substance use disorders, and gambling activates the reward system in brain in much the same way drugs do. Prevalence of gambling disorder in Japan is high rate because of slot machines and pachinko game are very popular in Japan. The author recommend group psychotherapy and self-help group (Gamblers Anonymous), because group dynamics make them accept their wrongdoings related to gambling and believe that they can enjoy their lives without gambling.

  4. Treatment of personality disorder.

    Science.gov (United States)

    Bateman, Anthony W; Gunderson, John; Mulder, Roger

    2015-02-21

    The evidence base for the effective treatment of personality disorders is insufficient. Most of the existing evidence on personality disorder is for the treatment of borderline personality disorder, but even this is limited by the small sample sizes and short follow-up in clinical trials, the wide range of core outcome measures used by studies, and poor control of coexisting psychopathology. Psychological or psychosocial intervention is recommended as the primary treatment for borderline personality disorder and pharmacotherapy is only advised as an adjunctive treatment. The amount of research about the underlying, abnormal, psychological or biological processes leading to the manifestation of a disordered personality is increasing, which could lead to more effective interventions. The synergistic or antagonistic interaction of psychotherapies and drugs for treating personality disorder should be studied in conjunction with their mechanisms of change throughout the development of each. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Rebecca E. Rosenberg

    2011-01-01

    Full Text Available We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD. Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder—not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.

  6. Attention Deficit Hyperactivity Disorder

    OpenAIRE

    Jaime O. Oliver

    2017-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is considered as among the most common yet serious brain disorders significant number of children are subjected to; the seriousness of which manifests in the ability of the disorder to continue to show up even after the childhood years, during the period of adolescence as well as adulthood. Considering the findings delivered by Brain Imaging Studies conducted on youth, it is revealed that people suffering from ADHD experiences del...

  7. EATING DISORDERS IN INDIA

    OpenAIRE

    Srinivasan, T.N.; Suresh, T.R.; Jayaram, Vasantha; Fernandez, M. Peter

    1995-01-01

    Data on the nature and extent of major eating disorders, anorexia nervosa and bulimia is lacking in non-white, native populations of the developing world, leaving a gap in understanding the determinants of these disorders. In a study on 210 medical students examined by a two-stage survey method, 31 subjects were found to have distress relating to their eating habits and body size not amounting to criterion-based diagnosis of eating disorders. The characteristics of this eating distress syndro...

  8. Treatment of Schizoaffective Disorder

    Science.gov (United States)

    2009-01-01

    In this article, we investigate the range of treatments prescribed for schizoaffective disorder. The data show that the majority of those treated, 87 percent, receive two or more pharmaceutical classes. From a therapeutic class perspective, 93 percent of schizoaffective disorder patients receive an antipsychotic, 48 percent receive a mood disorder treatment, and 42 percent receive an antidepressant. An expert commentary is also included. PMID:19724749

  9. Eating Disorders in Adolescents

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-10-01

    Full Text Available According to International Classification of Diseases by World Health Organization, eating disorders are behavioural syndromes associated with physiological disturbances [1]. Eating disorders include anorexia nervosa, atypical anorexia nervosa, bulimia nervosa, atypical bulimia nervosa, overeating associated with other psychological disturbances and vomiting associated with other psychological disturbances [1]. Maladaptive eating pattern and inadequate physical activity are seen in adolescents with eating disorders and obesity [2]. Those with comorbid eating disorder and obesity have a poorer prognosis and are at higher risk for future medical problems.

  10. Temporomandibular Disorders and Headache.

    Science.gov (United States)

    Graff-Radford, Steven B; Abbott, Jeremy J

    2016-08-01

    Temporomandibular disorders (TMD) and primary headaches can be perpetual and debilitating musculoskeletal and neurological disorders. The presence of both can affect up to one-sixth of the population at any one time. Initially, TMDs were thought to be predominantly musculoskeletal disorders, and migraine was thought to be solely a cerebrovascular disorder. The further understanding of their pathophysiology has helped to clarify their clinical presentation. This article focuses on the role of the trigeminal system in associating TMD and migraine. By discussing recent descriptions of prevalence, diagnosis, and treatment of headache and TMD, we will further elucidate this relationship. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Motility Disorders in Children.

    Science.gov (United States)

    Nurko, Samuel

    2017-06-01

    Gastrointestinal motility disorders in the pediatric population are common and can range from benign processes to more serious disorders. Performing and interpreting motility evaluations in children present unique challenges. There are primary motility disorders but abnormal motility may be secondary due to other disease processes. Diagnostic studies include radiographic scintigraphic and manometry studies. Although recent advances in the genetics, biology, and technical aspects are having an important impact and have allowed for a better understanding of the pathophysiology and therapy for gastrointestinal motility disorders in children, further research is needed to be done to have better understanding of the pathophysiology and for better therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Speech disorder prevention

    Directory of Open Access Journals (Sweden)

    Miladis Fornaris-Méndez

    2017-04-01

    Full Text Available Language therapy has trafficked from a medical focus until a preventive focus. However, difficulties are evidenced in the development of this last task, because he is devoted bigger space to the correction of the disorders of the language. Because the speech disorders is the dysfunction with more frequently appearance, acquires special importance the preventive work that is developed to avoid its appearance. Speech education since early age of the childhood makes work easier for prevent the appearance of speech disorders in the children. The present work has as objective to offer different activities for the prevention of the speech disorders.

  13. Addictive Disorders in Adolescents.

    Science.gov (United States)

    Truong, Anh; Moukaddam, Nidal; Toledo, Alexander; Onigu-Otite, Edore

    2017-09-01

    Addictive disorders in youth represent a dynamic field characterized by shifting patterns of substance use and high rates of experimentation, while retaining the risky behaviors and negative outcomes associated with established drug classes. Youth/adolescents are also at the forefront of use of new technologies, and non-substance-related disorders are pertinent. These disorders present with similar pictures of impairment, and can be diagnosed following the same principles. An underlying mental disorder and the possibility of a dual diagnosis need to be assessed carefully, and optimal treatment includes psychosocial treatments with applicable pharmacologic management, the latter representing an expanding field. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  15. Postoperative conversion disorder.

    Science.gov (United States)

    Afolabi, Kola; Ali, Sameer; Gahtan, Vivian; Gorji, Reza; Li, Fenghua; Nussmeier, Nancy A

    2016-05-01

    Conversion disorder is a psychiatric disorder in which psychological stress causes neurologic deficits. A 28-year-old female surgical patient had uneventful general anesthesia and emergence but developed conversion disorder 1 hour postoperatively. She reported difficulty speaking, right-hand numbness and weakness, and right-leg paralysis. Neurologic examination and imaging revealed no neuronal damage, herniation, hemorrhage, or stroke. The patient mentioned failing examinations the day before surgery and discontinuing her prescribed antidepressant medication, leading us to diagnose conversion disorder, with eventual confirmation by neuroimaging and follow-up examinations. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Attention deficit hyperactivity disorder and bipolar mood disorder in ...

    African Journals Online (AJOL)

    2009-06-19

    Jun 19, 2009 ... Bipolar mood disorder (BMD) has traditionally been seen as an adult disorder and .... antisocial behaviour, such as conduct disorder.3. In young ... In personality structure and temperament, children with BMD are more likely to ...

  17. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome

    Science.gov (United States)

    Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair

    2016-01-01

    Background SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. Methods We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. Results We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin–Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. Conclusions We thus propose that SOX11 deletion or mutation can present with a Coffin–Siris phenotype. PMID:26543203

  18. Social Anxiety Disorder

    Directory of Open Access Journals (Sweden)

    S Seedat

    2013-08-01

    Full Text Available According to epidemiological studies, rates of social anxiety disorder(SAD or social phobia range from 3% to 16% in the generalpopulation.[1,2]Social phobia and specific phobias have an earlier ageof onset than other anxiety disorders.

  19. Related Addictive Disorders.

    Science.gov (United States)

    Buck, Tina; Sales, Amos

    This paper provides an overview of addiction related to substance abuse. It provides basic information, prevalence, diagnostic criteria, assessment tools, and treatment issues for eating disorders, compulsive gambling, sex addictions, and work addictions. Eating disorders such as anorexia nervosa and bulimia nervosa, especially affect adolescents.…

  20. Disorders of visual perception

    NARCIS (Netherlands)

    Ffytche, Dominic H.; Blom, J. D.; Catani, M.

    Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders

  1. Female sexual arousal disorders

    NARCIS (Netherlands)

    Giraldi, Annamaria; Rellini, Alessandra H.; Pfaus, James; Laan, Ellen

    2013-01-01

    Definitions and terminology for female sexual arousal disorder (FSAD) are currently being debated. While some authors have suggested that FSAD is more a subjective response rather than a genital response, others have suggested that desire and arousal disorders should be combined in one entity.

  2. [DSM-5: neurodevelopmental disorders

    NARCIS (Netherlands)

    Zinkstok, J.; Buitelaar, J.K.

    2014-01-01

    BACKGROUND: The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in May, 2013. AIM: To review the changes in the diagnostic criteria for autism spectrum disorder (ASD) and ADHD in DSM-5, compared to DSM-IV. METHOD: The diagnostic criteria for ASD and ADHD

  3. Defining Oppositional Defiant Disorder

    Science.gov (United States)

    Rowe, Richard; Maughan, Barbara; Costello, E. Jane; Angold, Adrian

    2005-01-01

    Background: ICD-10 and DSM-IV include similar criterial symptom lists for conduct disorder (CD) and oppositional defiant disorder (ODD), but while DSM-IV treats each list separately, ICD-10 considers them jointly. One consequence is that ICD-10 identifies a group of children with ODD subtype who do not receive a diagnosis under DSM-IV. Methods: We…

  4. Body dysmorphic disorder

    NARCIS (Netherlands)

    Klatte, Julia; Vulink, Nienke; Kemperman, Patrick

    2016-01-01

    Body dysmorphic disorder (BDD) is a mental disorder by which the patient is obsessed with a perceived or minor defect in appearance, usually affecting the skin, hair, or nose, a defect hardly or not seen by others. This obsession can cause severe suffering and suicidality. Most patients consult a

  5. Disordered Gambling Prevalence

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Jessen, Lasse J.; Lau, Morten

    2018-01-01

    to all subjects and estimate prospective risk for disordered gambling. We find that 87.6% of the population is indicated for no detectable risk, 5.4% is indicated for early risk, 1.7% is indicated for intermediate risk, 2.6% is indicated for advanced risk, and 2.6% is indicated for disordered gambling...

  6. Autism Spectrum Disorder (ASD)

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Autism spectrum disorder (ASD) is a developmental disability that can cause ... work. Autism: What's New MMWR article: Prevalence of Autism Spectrum Disorder Data Community Report Press release: Autism Prevalence Slightly ...

  7. Disorder parameter of confinement

    International Nuclear Information System (INIS)

    Nakamura, N.; Ejiri, S.; Matsubara, Y.; Suzuki, T.

    1996-01-01

    The disorder parameter of confinement-deconfinement phase transition based on the monopole action determined previously in SU(2) QCD are investigated. We construct an operator which corresponds to the order parameter defined in the abelian Higgs model. The operator shows proper behaviors as the disorder parameter in the numerical simulations of finite temperature QCD. (orig.)

  8. Athletes with seizure disorders.

    Science.gov (United States)

    Knowles, Byron Don; Pleacher, Michael D

    2012-01-01

    Individuals with seizure disorders have long been restricted from participation in certain sporting activities. Those with seizure disorders are more likely than their peers to have a sedentary lifestyle and to develop obesity. Regular participation in physical activity can improve both physical and psychosocial outcomes for persons with seizure disorders. Seizure activity often is reduced among those patients who regularly engage in aerobic activity. Recent literature indicates that the diagnosis of seizure disorders remains highly stigmatizing in the adolescent population. Persons with seizure disorders may be more accepted by peer groups if they are allowed to participate in sports and recreational activities. Persons with seizure disorders are encouraged to participate in regular aerobic activities. They may participate in team sports and contact or collision activities provided that they utilize appropriate protective equipment. There seems to be no increased risk of injury or increasing seizure activity as the result of such participation. Persons with seizure disorders still are discouraged from participating in scuba diving and skydiving. The benefits of participation in regular sporting activity far outweigh any risk to the athlete with a seizure disorder who chooses to participate in sports.

  9. Eating Disorders and Sports.

    Science.gov (United States)

    Moriarty, Dick; Moriarty, Mary

    Since sports can sometimes lend themselves to eating disorders, coaches and sports administrators must get involved in the detection and treatment of this problem. While no reliable studies or statistics exist on the incidence of anorexia nervosa and/or bulimia among athletes, some research suggests that such disorders occur frequently among…

  10. Disorders of visual perception

    NARCIS (Netherlands)

    Ffytche, Dominic H.; Blom, J. D.; Catani, M.

    2010-01-01

    Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders

  11. Affective disorders among patients with borderline personality disorder.

    Science.gov (United States)

    Sjåstad, Hege Nordem; Gråwe, Rolf W; Egeland, Jens

    2012-01-01

    The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect

  12. Autistic disorder in 2 children with mitochondrial disorders.

    Science.gov (United States)

    Tsao, Chang-Yong; Mendell, Jerry R

    2007-09-01

    Autistic disorder is a heterogeneous disorder. The majority of the cases are idiopathic, and only a small number of the autistic children have associated secondary diagnosis. This article reports 2 children with mitochondrial disorders associated with autistic disorder fulfilling the diagnostic criteria of the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, and briefly reviews the literature on autistic disorder associated with mitochondrial disorders.

  13. Conduct disorders as a result of specific learning disorders

    OpenAIRE

    VOKROJOVÁ, Nela

    2012-01-01

    This thesis focuses on relationship between specific learning disorders and conduct disorders in puberty. The theoretical part explains the basic terms apearing in the thesis such as specific learning disorders, conduct disorders, puberty and prevention of conduct disorder formation. It presents Czech and foreign research which have already been done in this and related areas. The empirical part uses a quantitative method to measure anxiety and occurrence of conduct disorders in second grade ...

  14. Affective disorders among patients with borderline personality disorder.

    Directory of Open Access Journals (Sweden)

    Hege Nordem Sjåstad

    Full Text Available BACKGROUND: The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. METHODS: In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773, we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043 had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636. Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. RESULTS: More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. CONCLUSIONS: The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than

  15. Affective Disorders among Patients with Borderline Personality Disorder

    Science.gov (United States)

    Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

    2012-01-01

    Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

  16. Recurrence in affective disorder

    DEFF Research Database (Denmark)

    Kessing, L V; Olsen, E W; Andersen, P K

    1999-01-01

    The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward...... recurrence. The study base was the Danish psychiatric case register of all hospital admissions for primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of major affective disorder. For women with unipolar disorder and for all...... kinds of patients with bipolar disorder, the rate of recurrence was affected by the number of prior episodes even when the effect was adjusted for individual frailty toward recurrence. No effect of episodes but a large effect of the frailty parameter was found for unipolar men. The authors concluded...

  17. Female Sexual Arousal Disorders

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Rellini, Alessandra H; Pfaus, James

    2012-01-01

    Introduction.  Definitions and terminology for female sexual arousal disorder (FSAD) are currently being debated. While some authors have suggested that FSAD is more a subjective response rather than a genital response, others have suggested that desire and arousal disorders should be combined...... and psychological disorders, as well as to discuss different medical and psychological assessment and treatment modalities. Methods.  The experts of the International Society for Sexual Medicine's Standard Committee convened to provide a survey using relevant databases, journal articles, and own clinical experience....... Results.  Female Arousal Disorders have been defined in several ways with focus on the genital or subjective response or a combination of both. The prevalence varies and increases with increasing age, especially at the time of menopause, while distress decreases with age. Arousal disorders are often...

  18. Tourette disorder and other tic disorders.

    Science.gov (United States)

    Fernandez, Thomas V; State, Matthew W; Pittenger, Christopher

    2018-01-01

    Tourette disorder is a developmental neuropsychiatric condition characterized by vocal and motor tics that can range in severity from mild to disabling. It represents one end of a spectrum of tic disorders and is estimated to affect 0.5-0.7% of the population. Accumulated evidence supports a substantial genetic contribution to disease risk, but the identification of genetic variants that confer risk has been challenging. Positive findings in candidate gene association studies have not replicated, and genomewide association studies have not generated signals of genomewide significance, in large part because of inadequate sample sizes. Rare mutations in several genes have been identified, but their causality is difficult to establish. As in other complex neuropsychiatric disorders, it is likely that Tourette disorder risk involves a combination of common, low-effect and rare, larger-effect variants in multiple genes acting together with environmental factors. With the ongoing collection of larger patient cohorts and the emergence of affordable high-throughput genomewide sequencing, progress is expected to accelerate in coming years. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Heritable Disorders of Connective Tissue

    Science.gov (United States)

    ... Home Health Topics English Español Heritable Disorders of Connective Tissue Basics In-Depth Download Download EPUB Download PDF ... they? Points To Remember About Heritable Disorders of Connective Tissue There are more than 200 heritable disorders that ...

  20. Genetics Home Reference: bipolar disorder

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Bipolar disorder Bipolar disorder Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Bipolar disorder is a mental health condition that causes extreme ...

  1. Adrenal Gland Disorders: Condition Information

    Science.gov (United States)

    ... About Share Facebook Twitter Pinterest Email Print About Adrenal Gland Disorders The adrenal glands, located on the top of ... as estrogen and testosterone. What are adrenal gland disorders? Adrenal gland disorders occur when the adrenal glands do not ...

  2. Personality Disorders in patients with disorders in eating behaviors

    Directory of Open Access Journals (Sweden)

    Vanesa Carina Góngora

    2016-02-01

    Full Text Available The interest for the systematic study of personality disorder in patients with eating disorders starts in 1980 with the edition of the DSM III multiaxial classification system. Since then, several publications have been focused on the prevalence and the effect on treatment of personality disorders in bulimic and anorexic patients. These researches showed inconsistent results due to conceptual and methodological divergences. In this paper, the more relevant findings of these studies are presented and the possible sources of discrepancy are analyzed. In general, there is a moderate comorbidity between personality disorders and eating disorders. The most frequent disorders are borderline, histrionic, obsessive-compulsive, dependent and avoidant personality disorders. Borderline and histrionic personality disorders are more frequently associated with bulimia, whereas avoidant and obsessive- compulsive personality disorders are more characteristic of anorexia nervosa. Nevertheless, the effect of the relationship between eating disorders and personality disorders in treatment remains uncertain, giving raise to several controversies and researches. 

  3. Epilepsy and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2012-03-01

    Full Text Available Mood disorders are the most common psychiatric comorbid disorder that affects quality of life and prognosis in epilepsy. The relation between depression and epilepsy is bidirectional. Not only the risk of having a depression among epilepsy cases is more than the healthy control cases, but also the risk of having epilepsy among depressive cases is more than the healthy control cases. People diagnosed with epilepsy are five times more likely than their peers to commit suicide. Moreover it seems that some epilepsy types like temporal lobe epilepsy have a much higher risk (25 times for suicide. Risk of suicide in epilepsy, which is independent from depression, increases more with the presence of depression. The common pathway between epilepsy, depression and suicide is hypofrontality and irregularity of serotonin metabolism. Contrary to depression, data on relationship between bipolar disorder and epilepsy is limited. However, mood disorder, mixed episodes with irritable character and mania are more frequent than assumed. As a matter of fact, both disorders share some common features. Both are episodic and can become chronic. Kindling phenomenon, irregularities in neurotransmitters, irregularities in voltage gate ion channels and irregularities in secondary messenger systems are variables that are presented in the etiologies of both disorders. Anticonvulsant drugs with mood regulatory effects are the common points of treatment. Understanding their mechanisms of action will clarify the pathophysiological processes. In this article, the relationhip between epilepsy and mood disorders, comorbidity, secondary states and treatment options in both cases have been discussed.

  4. Cardiomyopathy in neurological disorders.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. The cerebellum and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Joseph ePhillips

    2015-05-01

    Full Text Available The cerebellum has been considered for a long time to play a role solely in motor coordination. However, studies over the past two decades have shown that the cerebellum also plays a key role in many motor, cognitive, and emotional processes. In addition, studies have also shown that the cerebellum is implicated in many psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. In this review, we discuss existing studies reporting cerebellar dysfunction in various psychiatric disorders. We will also discuss future directions for studies linking the cerebellum to psychiatric disorders.

  6. Kinetics of tetrataenite disordering

    International Nuclear Information System (INIS)

    Dos Santos, E.; Gattacceca, J.; Rochette, P.; Fillion, G.; Scorzelli, R.B.

    2015-01-01

    Tetrataenite is a chemically ordered L1 0 -type Fe 50 Ni 50 alloy detected for the first time in 1977 by 57 Fe Mössbauer spectroscopy studies in iron meteorites. The thermal history of meteorites, in particular short thermal events like those associated to hypervelocity impacts, can be constrained by tracing the presence of tetrataenite or its disordering into taenite. The knowledge of the disordering kinetics of tetrataenite, that is associated with changes in its magnetic properties, is still very fragmentary so that the time–temperature history of these meteorites cannot be constrained in details. Furthermore, knowledge of disordering kinetics is important due to potential technological application of tetrataenite as a rare-earth free strong magnet. Thus, this work provides the first time–temperature data for disordering reaction of tetrataenite. We have shown that disordering is not an instantaneous process but is a kinetic limited reaction. It was shown that disordering may take place at any temperature above the order–disorder transition for L 10 superstructure phase (∼320 °C) when the appropriate time-scale is considered. This result means that the apparent Curie point for tetrataenite is not an absolute property in the sense that any estimate of this parameter should be referred to a given time-scale. - Highlights: • The first time–temperature data for tetrataenite disordering reaction is provided. • Previous works does not give a complete picture of tetrataenite disordering. • Apparent Curie temperature of tetrataenite should be referred to a time-scale. • Tetrataenite can be used as a probe to detect thermal/shock events recorded in meteorites

  7. Body dysmorphic disorder

    DEFF Research Database (Denmark)

    Jawad, Mustafa Bashir M; Sjögren, Magnus

    2017-01-01

    Body dysmorphic disorder is defined by a preoccupation of one or more non-existent or slight defects or flaws in the physical appearance. The prevalence is 1.7-2.4% in the general population with a higher incidence rate in women. The rate of suicidal ideation is as high as 80%, and up to 25......% of the patients attempt to commit suicide. Comorbidities, such as obsessive compulsive disorder, depression, and anxiety, are frequent. These patients may seek cosmetic or dermatologic rather than psychological treatment. In the view of the high prevalence and risk of suicide, recognizing this disorder...

  8. [Antisocial personality disorder].

    Science.gov (United States)

    Repo-Tiihonen, Eila; Hallikainen, Tero

    2016-01-01

    Antisocial personality disorder (ASP), especially psychopathy as its extreme form, has provoked fear and excitement over thousands of years. Ruthless violence involved in the disorder has inspired scientists, too.The abundance of research results concerning epidemiology, physiology, neuroanatomy, heritability, and treatment interventions has made ASP one of the best documented disorders in psychiatry. Numerous interventions have been tested, but there is no current treatment algorithm. Biological and sociological parameters indicate the importance of early targeted interventions among the high risk children. Otherwise, as adults they cause the greatest harm. The use of medications or psychotherapy for adults needs careful consideration.

  9. Ghrelin and Eating Disorders

    Science.gov (United States)

    Atalayer, Deniz; Gibson, Charlisa; Konopacka, Alexandra; Geliebter, Allan

    2012-01-01

    There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders. PMID:22960103

  10. Body Dysmorphic Disorder

    Directory of Open Access Journals (Sweden)

    Perihan Cam Ray

    2012-12-01

    Full Text Available Body dysmorphic disorder is a type of mental illness, wherein the affected person is concerned with body image, manifested as excessive concern about and preoccupation with a perceived defect of their physical features. Although it is a common disease and has been defined in the literature over a century, it is not a well known disease. Chronic, treatment resistant and sometimes delusional nature could result in severe functional impairment. The diagnosis and appropriate therapy of disorder are crucial because of increased suicidality and reduction in life quality. In this article the symptoms, etiology, clinical features and treatment of body dysmorphic disorder are briefly reviewed.

  11. [Clothing and heat disorder].

    Science.gov (United States)

    Satsumoto, Yayoi

    2012-06-01

    The influence of the clothing material properties(like water absorbency and rapid dryness, water vapor absorption, water vapor permeability and air permeability) and the design factor of the clothing(like opening condition and fitting of clothing), which contributed to prevent heat disorder, was outlined. WBGT(wet-bulb globe temperature) is used to show a guideline for environmental limitation of activities to prevent heat disorder. As the safety function is more important than thermal comfort for some sportswear and protective clothing with high cover area, clothing itself increases the risk of heat disorder. WBGT is corrected by CAF (clothing adjustment factor) in wearing such kind of protective clothing.

  12. Delusional disorder-somatic type (or body dysmorphic disorder) and ...

    African Journals Online (AJOL)

    With regard to delusional disorder-somatic subtype there may be a relationship with body dysmorphic disorder. There are reports that some delusional disorders can evolve to become schizophrenia. Similarly, the treatment of such disorders with antipsychotics has been documented. This report describes a case of ...

  13. Sleep disorders in children with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Medina Permatawati

    2018-03-01

    Conclusion The proportion of sleep disorder in children with ADHD is relatively high, with the majority having a disorder of initiating and maintaining sleep. Children with combined type ADHD experience a higher amount of sleep disorder than those with either the inattention or hyperactive-impulsive types of ADHD. Children with poor sleep hygiene have significantly more severe sleep disorders.

  14. Dementia in affective disorder

    DEFF Research Database (Denmark)

    Kessing, L V; Olsen, E W; Mortensen, P B

    1999-01-01

    OBJECTIVE: The aim of the study was to investigate whether patients with affective disorder have increased risk of developing dementia compared to other groups of psychiatric patients and compared to the general population. METHOD: In the Danish psychiatric central register, 3363 patients...... with unipolar affective disorder, 518 patients with bipolar affective disorder, 1025 schizophrenic and 8946 neurotic patients were identified according to the diagnosis at the first ever discharge from psychiatric hospital during the period from 1970 to 1974. The rate of discharge diagnosis of dementia...... on readmission was estimated during 21 years of follow-up. In addition, the rates were compared with the rates for admission to psychiatric hospitals with a discharge diagnosis of dementia for the total Danish population. RESULTS: Patients with unipolar and with bipolar affective disorder had a greater risk...

  15. SOCIAL ANXIETY DISORDER

    African Journals Online (AJOL)

    substance abuse, and the disorder impacts significantly on social and ... characteristic fear of social and performance situations where exposure to unfamiliar ... concomitant therapy from psychoactive medications other than chloral hydrate; if ...

  16. What is Bipolar Disorder?

    Science.gov (United States)

    ... down” Have trouble sleeping Think about death or suicide Can someone have bipolar disorder along with other problems? Yes. Sometimes people having very strong mood episodes may have psychotic symptoms. Psychosis affects thoughts ...

  17. Skin Pigmentation Disorders

    Science.gov (United States)

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  18. Disruptive Behavior Disorders

    Science.gov (United States)

    ... Ribbon Commands Skip to main content Turn off Animations Turn on Animations Our Sponsors Log in | Register Menu Log in | ... greater chance of experiencing learning disabilities such as reading disorders and verbal impairment. But what distinguishes children ...

  19. Sleep Disorders (PDQ)

    Science.gov (United States)

    ... Types of Cancer Treatment Surgery Radiation Therapy External Beam Radiation Internal Radiation Therapy Side Effects Chemotherapy Immunotherapy ... asleep, sleeping, or waking from sleep, such as walking, talking, or eating. Sleep disorders keep you from ...

  20. Functional Movement Disorder

    Science.gov (United States)

    ... Publications Patient Organizations International Parkinson and Movement Disorder Society National Institute of Mental Health (NIMH) See all related organizations Publications Order NINDS Publications Definition Psychogenic movement is an unwanted muscle movement such ...

  1. Temporomandibular Joint Disorder

    Science.gov (United States)

    ... Baby Bottle Tooth Decay? Pacifiers Have Negative and Positive Effects What is Dental Amalgam (Silver Filling)? Check Menstrual Calendar for Tooth Extraction Temporomandibular Joint Disorder Learn what those dental words mean. Check out how your teeth and mouth ...

  2. Adrenal Gland Disorders

    Science.gov (United States)

    ... Cushing's syndrome, there's too much cortisol, while with Addison's disease, there is too little. Some people are born unable to make enough cortisol. Causes of adrenal gland disorders include Genetic mutations Tumors ...

  3. Autism Spectrum Disorder

    Centers for Disease Control (CDC) Podcasts

    This podcast discusses autism spectrum disorder (ASD), a developmental disability that causes problems with social, communication, and behavioral skills. CDC estimates that one in 68 children has been identified as having ASD.

  4. Schizophrenia: A Systemic Disorder

    Science.gov (United States)

    Kirkpatrick, Brian; Miller, Brian; García-Rizo, Clemente; Fernandez-Egea, Emilio

    2015-01-01

    The concept of schizophrenia that is most widely taught is that it is a disorder in which psychotic symptoms are the main problem, and a dysregulation of dopamine signaling is the main feature of pathophysiology. However, this concept limits clinical assessment, the treatments offered to patients, research, and the development of therapeutics. A more appropriate conceptual model is that: 1) schizophrenia is not a psychotic disorder, but a disorder of essentially every brain function in which psychosis is present; 2) it is not a brain disease, but a disorder with impairments throughout the body; 3) for many patients, neuropsychiatric problems other than psychosis contribute more to impairment in function and quality of life than does psychosis; and, 4) some conditions that are considered to be comorbid are integral parts of the illness. In conclusion, students, patients, and family members should be taught this model, along with its implications for assessment, research, and therapeutics. PMID:23518782

  5. Fetal Alcohol Spectrum Disorders

    Science.gov (United States)

    Alcohol can harm your baby at any stage during a pregnancy. That includes the earliest stages, before ... can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Children who are born with ...

  6. Bipolar disorder: an update

    African Journals Online (AJOL)

    lifetime incidence), recurrent mood disorder, with strong genetic undertones ... self-esteem/grandiosity, significantly decreased need for sleep, racing speech .... chaperone protein, GRP 78.26 Valproate's effects on DNA histone acetylation may ...

  7. Acquired bleeding disorders

    African Journals Online (AJOL)

    B one marrow aplasia ... Laboratory approach to a suspected acquired bleeding disorder. (LER = leuko- .... lymphocytic leukaemia, and lymphoma). ... cells), a bone marrow aspirate and trephine biopsy (BMAT) is not ..... transplantation.

  8. Dimorphism and patellofemoral disorders.

    Science.gov (United States)

    Arendt, Elizabeth A

    2006-10-01

    Sex is defined as the classification of living things according to their chromosomal compliment. Gender is defined as a person's self-representation as a male or female or how social institutions respond to that person on the basis of his or her gender presentation. One frequently divides the topic or dimorphism into the biologic response inherent in their sex and the environmental response that might be better termed "gender differences." Clinicians have anecdotally agreed for years that patellofemoral disorders are more common in women. Given the difficulty in classifying patellofemoral disorders, literature support for this assumption is meager. For the purposes of this article we divide patellofemoral disorders into three categories: patellofemoral pain, patellofemoral instability, and patellofemoral arthritis. possible sex difference in these disorders are reviewed.

  9. Screening for Panic Disorder

    Science.gov (United States)

    ... Print this form Follow Us Facebook Twitter RSS YouTube Advertisement Find A Therapist Search our directory of ADAA mental health professional members who specialize in anxiety, depression and co-occurring disorders. Understand the Facts Anxiety ...

  10. Anxiety Disorders: Support Groups

    Science.gov (United States)

    ... overall treatment regimen. Follow Us Facebook Twitter RSS YouTube Advertisement Find A Therapist Search our directory of ADAA mental health professional members who specialize in anxiety, depression and co-occurring disorders. Understand the Facts Anxiety ...

  11. Treatment for Anxiety Disorders

    Science.gov (United States)

    ... finding a therapist . Follow Us Facebook Twitter RSS YouTube Advertisement Advertisement Find A Therapist Search our directory of ADAA mental health professional members who specialize in anxiety, depression and co-occurring disorders. Understand the Facts Anxiety ...

  12. Developmental coordination disorder

    Science.gov (United States)

    Developmental coordination disorder can lead to: Learning problems Low self-esteem resulting from poor ability at sports and teasing by other children Repeated injuries Weight gain as a result of not wanting to participate ...

  13. Intermittent Explosive Disorder

    Science.gov (United States)

    ... explosive disorder involves repeated, sudden episodes of impulsive, aggressive, violent behavior or angry verbal outbursts in which you react grossly out of proportion to the situation. Road rage, domestic abuse, throwing or breaking objects, or other temper tantrums ...

  14. Disruptive Mood Dysregulation Disorder

    Science.gov (United States)

    ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home Research ... Chat on Disruptive Mood Dysregulation Disorder (Archived Transcript) Research and ... Journal Articles: References and abstracts from MEDLINE/PubMed (National ...

  15. Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Matthews, Marguerite; Nigg, Joel T.

    2014-01-01

    Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder’s pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID:24214656

  16. Flocking through disorder

    Science.gov (United States)

    Morin, Alexandre; Desreumaux, Nicolas; Caussin, Jean-Baptiste; Bartolo, Denis

    How do flocks, herds and swarms proceed through disordered environments? This question is not only crucial to animal groups in the wild, but also to virtually all applications of collective robotics, and active materials composed of synthetic motile units. In stark contrast, appart from very rare exceptions, our physical understanding of flocking has been hitherto limited to homogeneous media. Here we explain how collective motion survives to geometrical disorder. To do so, we combine experiments on motile colloids cruising through random microfabricated obstacles, and analytical theory. We explain how disorder and bending elasticity compete to channel the flow of polar flocks along sparse river networks akin those found beyond plastic depinning in driven condensed matter. Further increasing disorder, we demonstrate that collective motion is suppressed in the form of a first-order phase transition generic to all polar active materials.

  17. Autism Spectrum Disorder (ASD)

    Science.gov (United States)

    ... within the category. These were autistic disorder ("classic" autism), Asperger syndrome (which usually involved milder symptoms, mostly related ... but not all, of the features of classic autism or Asperger syndrome). 2 Health care providers no longer use ...

  18. Autonomic Nervous System Disorders

    Science.gov (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  19. Depressive and bipolar disorders

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Hansen, Hanne Vibe; Demyttenaere, Koen

    2005-01-01

    of the patients (40-80%) had erroneous views as to the effect of antidepressants. Older patients (over 40 years of age) consistently had a more negative view of the doctor-patient relationship, more erroneous ideas concerning the effect of antidepressants and a more negative view of antidepressants in general....... Moreover, their partners agreed on these negative views. Women had a more negative view of the doctor-patient relationship than men, and patients with a depressive disorder had a more negative view of antidepressants than patients with bipolar disorder. The number of psychiatric hospitalizations......BACKGROUND: There is increasing evidence that attitudes and beliefs are important in predicting adherence to treatment and medication in depressive and bipolar disorders. However, these attitudes have received little study in patients whose disorders were sufficiently severe to require...

  20. Psychoneuroimmunology of mental disorders.

    Science.gov (United States)

    Soria, Virginia; Uribe, Javiera; Salvat-Pujol, Neus; Palao, Diego; Menchón, José Manuel; Labad, Javier

    The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Hearing Disorders and Deafness

    Science.gov (United States)

    ... enough to enjoy talking with friends or family. Hearing disorders make it hard, but not impossible, to ... often be helped. Deafness can keep you from hearing sound at all. What causes hearing loss? Some ...

  2. Binge Eating Disorder

    Science.gov (United States)

    ... himself. Understanding Binge Eating If you gorged on chocolate during Halloween or ate so much pumpkin pie ... binge eating, doctors may prescribe medications along with therapy and nutrition advice. People with binge eating disorder ...

  3. Order-Disorder Theory

    International Nuclear Information System (INIS)

    Kasteleyn, P.W.

    1971-01-01

    Apology. 1. Order-disorder transitions; 2. The Ising model; 3. The classical theories; 4. The exact analysis of the Ising model; 5. Series expansions; 6. Relations between critical indices; 7. Other models; 8. Concluding remarks. (author)

  4. Child Behavior Disorders

    Science.gov (United States)

    ... a death in the family may cause a child to act out. Behavior disorders are more serious. ... The behavior is also not appropriate for the child's age. Warning signs can include Harming or threatening ...

  5. Schizoid personality disorder

    Directory of Open Access Journals (Sweden)

    Gerhard Dammann

    2017-11-01

    Full Text Available The schizoid personality disorder is characterized by a lack of interest in close relationships, both in the family and in other interpersonal relationships, including intimate/sexual interactions, a superiority of introverted activities, emotional coldness, estrangement and flattened affect (DSM-5. This video lecture is devoted to the review of the prevalence, diagnosis, and treatment of this disorder. In addition, the lecture examines clinical cases and an example of managing such patients.

  6. Coagulation and Mental Disorders

    Directory of Open Access Journals (Sweden)

    Silvia Hoirisch-Clapauch

    2014-10-01

    Full Text Available The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.

  7. Mood disorders: neurocognitive models.

    Science.gov (United States)

    Malhi, Gin S; Byrow, Yulisha; Fritz, Kristina; Das, Pritha; Baune, Bernhard T; Porter, Richard J; Outhred, Tim

    2015-12-01

    In recent years, a number of neurocognitive models stemming from psychiatry and psychology schools of thought have conceptualized the pathophysiology of mood disorders in terms of dysfunctional neural mechanisms that underpin and drive neurocognitive processes. Though these models have been useful for advancing our theoretical understanding and facilitating important lines of research, translation of these models and their application within the clinical arena have been limited-partly because of lack of integration and synthesis. Cognitive neuroscience provides a novel perspective for understanding and modeling mood disorders. This selective review of influential neurocognitive models develops an integrative approach that can serve as a template for future research and the development of a clinically meaningful framework for investigating, diagnosing, and treating mood disorders. A selective literature search was conducted using PubMed and PsychINFO to identify prominent neurobiological and neurocognitive models of mood disorders. Most models identify similar neural networks and brain regions and neuropsychological processes in the neurocognition of mood, however, they differ in terms of specific functions attached to neural processes and how these interact. Furthermore, cognitive biases, reward processing and motivation, rumination, and mood stability, which play significant roles in the manner in which attention, appraisal, and response processes are deployed in mood disorders, are not sufficiently integrated. The inclusion of interactions between these additional components enhances our understanding of the etiology and pathophysiology of mood disorders. Through integration of key cognitive functions and understanding of how these interface with neural functioning within neurocognitive models of mood disorders, a framework for research can be created for translation to diagnosis and treatment of mood disorders. © 2015 John Wiley & Sons A/S. Published by John

  8. [Premenstrual Dysphoric Disorder (PMDD)].

    Science.gov (United States)

    Yamada, Kazuo

    2015-01-01

    Premenstrual dysphoric disorder (PMDD) is categorized as a subclass in depressive disorders of DSM-5. Speaking without fear of misunderstanding, my opinion is that patients with PMDD should be treated with medication, if there is no misdiagnosis as premenstrual syndrome (PMS). For the appropriate treatment of PMDD, it must be diagnosed accurately according to the DSM-5 criteria. The differential diagnosis and treatment of PMDD should be carried out by experienced psychiatrists.

  9. Sleep disorders in psychiatry.

    Science.gov (United States)

    Costa e Silva, Jorge Alberto

    2006-10-01

    Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal

  10. Aquatherapy for neurodegenerative disorders.

    Science.gov (United States)

    Plecash, Alyson R; Leavitt, Blair R

    2014-01-01

    Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

  11. Immune disorders in anorexia

    OpenAIRE

    SŁOTWIŃSKA, SYLWIA MAŁGORZATA; SŁOTWIŃSKI, ROBERT

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters pla...

  12. Genotyping Sleep Disorders Patients

    OpenAIRE

    Kripke, Daniel F.; Shadan, Farhad F.; Dawson, Arthur; Cronin, John W.; Jamil, Shazia M.; Grizas, Alexandra P.; Koziol, James A.; Kline, Lawrence E.

    2010-01-01

    Objective The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting. Methods To assess the validity of several candidate associations, we obtained saliva deoxyribonucleic acid (DNA) samples and clinical information from 360 consenting research p...

  13. Night Eating Disorders

    OpenAIRE

    Deniz Tuncel; Fatma Özlem Orhan

    2009-01-01

    Hunger is an awakening related biological impulse. The relationship between hunger and sleep is moderated by the control of homeostatic and circadian rhytms of the body. Abnormal eating behavior during sleep period could result from different causes. Abnormal eating during the main sleep period has been categorized as either night eating syndrome or sleep related eating disorder. Night eating syndrome (NES) is an eating disorder characterised by the clinical features of morning anorexia, even...

  14. Eating disorders and personality

    OpenAIRE

    Levallius, Johanna

    2018-01-01

    Eating disorders are serious psychiatric conditions often demanding specialized psychiatric care. Several effective treatments have been developed and disseminated, but more needs to be done, as not all patients respond well to intervention, let alone achieve recovery. Obvious candidates such as eating disorder diagnosis, symptoms and psychiatric comorbidity have generally failed to explain variability in prognosis and outcome, warranting investigation of a wider range of relevant factors. Ac...

  15. Myelination and myelin disorders

    International Nuclear Information System (INIS)

    Knaap, M.S. van der.

    1991-01-01

    The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1 H and 31 P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs

  16. Sleep disorders in children

    OpenAIRE

    Montgomery, Paul; Dunne, Danielle

    2007-01-01

    Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  17. Sleep disorders in children

    OpenAIRE

    Bruni, Oliveiero; Novelli, Luana

    2010-01-01

    Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  18. Stigma and mood disorders.

    Science.gov (United States)

    Kelly, Claire M; Jorm, Anthony F

    2007-01-01

    To update the reader on current research on stigmatizing attitudes towards people suffering from mood disorders and to describe recent interventions in this area. The public generally feels their own attitudes are more favourable to people with depression than 'most other people's' attitudes are. Among those with depressive symptoms, self-stigma in relation to depression is higher than perceived stigma from others, including professionals, thus hindering help seeking. The main factor that seems to improve the attitudes towards people with any mental illness is personal contact. Moderate improvements in attitudes have been achieved with an online intervention. Caution must be taken when ensuring that improvements in knowledge about mental disorders do not lead to increased social distance. There exists little research on stigmatizing attitudes towards people with mood disorders. Most of the literature on the stigma towards people with mental illness relates to people with more severe disorders such as schizophrenia. When research has been done on mood disorders, the focus has been on perceived stigma and self-stigma. No up-to-date research exists on discrimination experienced by people with mood disorders, and very little research exists on interventions designed to decrease stigmatizing attitudes towards them.

  19. Eating disorders in women

    Science.gov (United States)

    Sharan, Pratap; Sundar, A. Shyam

    2015-01-01

    Eating disorders, especially anorexia nervosa and bulimia nervosa have been classically described in young females in Western population. Recent research shows that they are also seen in developing countries including India. The classification of eating disorders has been expanded to include recently described conditions like binge eating disorder. Eating disorders have a multifactorial etiology. Genetic factor appear to play a major role. Recent advances in neurobiology have improved our understanding of these conditions and may possibly help us develop more effective treatments in future. Premorbid personality appears to play an important role, with differential predisposition for individual disorders. The role of cultural factors in the etiology of these conditions is debated. Culture may have a pathoplastic effect leading to non-conforming presentations like the non fat-phobic form of anorexia nervosa, which are commonly reported in developing countries. With rapid cultural transformation, the classical forms of these conditions are being described throughout the world. Diagnostic criteria have been modified to accommodate for these myriad presentations. Treatment of eating disorders can be quite challenging, given the dearth of established treatments and poor motivation/insight in these conditions. Nutritional rehabilitation and psychotherapy remains the mainstay of treatment, while pharmacotherapy may be helpful in specific situations. PMID:26330646

  20. Women's sexual pain disorders.

    Science.gov (United States)

    van Lankveld, Jacques J D M; Granot, Michal; Weijmar Schultz, Willibrord C M; Binik, Yitzchak M; Wesselmann, Ursula; Pukall, Caroline F; Bohm-Starke, Nina; Achtrari, Chahin

    2010-01-01

    Women's sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area. To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and treatment of women's sexual pain disorders. An expert committee, invited from six countries by the 3rd International Consultation, was comprised of eight researchers and clinicians from biological and social science disciplines, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of women's sexual pain disorders. Expert opinion was based on grading of evidence-based medical literature, extensive internal committee discussion, public presentation, and debate. Results. A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence-based recommendations for assessment of women's sexual pain disorders are reviewed. An evidence-based approach to management of these disorders is provided. Continued efforts are warranted to conduct research and scientific reporting on the optimal assessment and management of women's sexual pain disorders, including multidisciplinary approaches.

  1. Vertigo and metabolic disorders.

    Science.gov (United States)

    Santos, Maruska D' Aparecida; Bittar, Roseli Saraiva Moreira

    2012-01-01

    Metabolic disorders are accepted by many authors as being responsible for balance disorders. Because of the importance of metabolic disorders in the field of labyrinthine dysfunction, we decided to assess the prevalence of carbohydrates, lipids and thyroid hormones disorders in our patients with vestibular diseases. The study evaluates the metabolic profile of 325 patients with vertigo who sought the Otolaryngology Department of the University of São Paulo in the Hospital das Clínicas da Universidade de São Paulo. The laboratory tests ordered according to the classical research protocol were: low-density lipoprotein cholesterol fraction, TSH, T3, T4 and fasting blood sugar level. The metabolic disorders found and the ones that were observed in the general population were compared. The high level of low-density lipoprotein cholesterol, the altered levels of thyroid hormones, the higher prevalence of diabetes mellitus were the most significant changes found in the group of study. The higher amount of metabolic disorders in patients with vertigo disease reinforces the hypothesis of its influence on the etiopathogenesis of cochleovestibular symptoms.

  2. Skin Picking Disorder

    Directory of Open Access Journals (Sweden)

    Pinar Cetinay Aydin

    2014-08-01

    Full Text Available Skin picking disorder is not a dermatological disorder and it is a table characterized with picking skin excessively and repetitively, leading to damage in skin tissue. Unlike normal picking behaviour, psychogenic skin picking is repetitive and it can lead to severe damage in the skin and even complications which constitute vital danger. While some patients define frequent but short lasting picking attacks, others define rarer attacks which last a few hours. Skin picking disorder, which is not included in the classification systems up to DSM-5 as a separate diagnosis category, is included as an independent diagnosis in Obsessive Compulsive Disorder and Associated Disorders category in DSM-5. In case reports, open label studies and double blind studies selective serotonin reuptake inhibitors are shown to be effective in the treatment of skin picking disorder. Mostly, cognitive-behaviourial techniques are used and have been proven to be useful in psychotherapy. Habit reversal is one of the behaviourial techniques which are frequently applied, give positive results in which well-being state can be maintained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 401-428

  3. Dyslipidemia in Dermatological Disorders

    Science.gov (United States)

    Shenoy, Chetana; Shenoy, Manjunath Mala; Rao, Gururaja K.

    2015-01-01

    Dyslipidemias are one of the common metabolic disorders. A link between dermatological disorders like psoriasis and dyslipidemia has been established in the recent past. Many dermatological disorders could have a systemic inflammatory component which explains such association. Chronic inflammatory dermatological disorders could also have other metabolic imbalances that may contribute to dyslipidemia. Presence of such abnormal metabolism may justify routine screening of these disorders for associated dyslipidemia and other metabolic abnormalities and early treatment of such comorbidities to improve quality of life. Some of the drugs used by dermatologists such as retinoids are also likely to be a cause of dyslipidemia. Hence, it is imperative that the dermatologists obtain scientific knowledge on the underlying mechanisms involved in dyslipidemia and understand when to intervene with therapies. A systematic review of the English language literature was done by using Google Scholar and PubMed. In this review, attempts are made to list the dermatological disorders associated with dyslipidemia; to simplify the understanding of underlying mechanisms; and to give a brief idea about the interventions. PMID:26713286

  4. Suicidal Behavior in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Bedriye Oncu

    2013-03-01

    Full Text Available Suicide associated mortality rates are notable for eating disorders. Crude mortality rate associated with suicide, varies between 0% and 5.3% in patients with eating disorders. Prominent risk factors for suicidal behavior among these patients are subtype of the eating disorders, comorbid psychiatric diagnosis (e.g. depression, alcohol and substance abuse, personality disorders, ultrarapid drug metabolism, history of childhood abuse and particular family dynamics. In this article, suicidal behavior and associated factors in eating disorders are briefly reviewed.

  5. The continuum between Bipolar Disorder and Borderline Personality Disorder.

    Science.gov (United States)

    Elisei, Sandro; Anastasi, Serena; Verdolini, Norma

    2012-09-01

    Several studies have been carried out regarding the possible overlap between Bipolar Disorder and borderline personality disorder. Up to now, it is not possible to provide a definitive picture. In fact, there is currently significant debate about the relationship between Borderline Personality Disorder and Bipolar Disorder. MEDLINE searches were performed to identify the latest studies of these disorders, considering psychodynamic aspects. Bipolar disorder and borderline personality disorder share common clinical features, namely affective instability and impulsivity which however differ in quality. Consequently, to better understand these aspects, it is necessary to trace the stages of childhood psychological development. It has been claimed that Bipolar Disorder Type II can be divided into two subtypes: one stable and functional between episodes and one unstable between episodes which is related to Borderline Personality Disorder. However, better diagnostic theories, psychiatrist's empathy and patience remain the essential tool to understand and to face human suffering.

  6. Clinical status of comorbid bipolar disorder and borderline personality disorder.

    Science.gov (United States)

    Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

    2016-09-01

    The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

  7. Self-disorders in schizophrenia-spectrum disorders

    DEFF Research Database (Denmark)

    Nordgaard, Julie; Nilsson, Lars Siersbæk; Sæbye, Ditte

    2017-01-01

    Self-disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia-spectrum disorders and a certain degree of temporal stability of self-disorders would therefore be expected. The aim of the study was to examine the persistence of self-disorders measured...... by the Examination of Anomalous Self Experiences over a time span of 5 years. 48 patients with schizophrenia-spectrum disorders were thoroughly assessed for psychopathology at baseline and 5 years later. Self-disorders were assessed by the Examination of Anomalous Self Experiences. The level of self-disorders...... was same at the two occasions for the full Examination of Anomalous Self Disorders and for four out of the five domains. For one domain, the level of self-disorders increased slightly from baseline to follow-up. The correlations between baseline and follow-up were moderate. 9 out of the 13 most...

  8. Attention-deficit hyperactivity disorder and anxiety disorders as precursors of bipolar disorder onset in adulthood

    DEFF Research Database (Denmark)

    Meier, Sandra M; Pavlova, Barbara; Dalsgaard, Søren

    2018-01-01

    BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and anxiety disorders have been proposed as precursors of bipolar disorder, but their joint and relative roles in the development of bipolar disorder are unknown.AimsTo test the prospective relationship of ADHD and anxiety with onset...... of bipolar disorder. METHOD: We examined the relationship between ADHD, anxiety disorders and bipolar disorder in a birth cohort of 2 409 236 individuals born in Denmark between 1955 and 1991. Individuals were followed from their sixteenth birthday or from January 1995 to their first clinical contact...... for bipolar disorder or until December 2012. We calculated incidence rates per 10 000 person-years and tested the effects of prior diagnoses on the risk of bipolar disorder in survival models. RESULTS: Over 37 394 865 person-years follow-up, 9250 onsets of bipolar disorder occurred. The incidence rate...

  9. Neuroimaging in eating disorders

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2011-09-01

    Full Text Available Ignacio Jáuregui-LoberaBehavioral Sciences Institute and Pablo de Olavide University, Seville, SpainAbstract: Neuroimaging techniques have been useful tools for accurate investigation of brain structure and function in eating disorders. Computed tomography, magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy, and voxel-based morphometry have been the most relevant technologies in this regard. The purpose of this review is to update the existing data on neuroimaging in eating disorders. The main brain changes seem to be reversible to some extent after adequate weight restoration. Brain changes in bulimia nervosa seem to be less pronounced than in anorexia nervosa and are mainly due to chronic dietary restrictions. Different subtypes of eating disorders might be correlated with specific brain functional changes. Moreover, anorectic patients who binge/purge may have different functional brain changes compared with those who do not binge/purge. Functional changes in the brain might have prognostic value, and different changes with respect to the binding potential of 5-HT1A, 5-HT2A, and D2/D3 receptors may be persistent after recovering from an eating disorder.Keywords: neuroimaging, brain changes, brain receptors, anorexia nervosa, bulimia nervosa, eating disorders

  10. Night Eating Disorders

    Directory of Open Access Journals (Sweden)

    Deniz Tuncel

    2009-08-01

    Full Text Available Hunger is an awakening related biological impulse. The relationship between hunger and sleep is moderated by the control of homeostatic and circadian rhytms of the body. Abnormal eating behavior during sleep period could result from different causes. Abnormal eating during the main sleep period has been categorized as either night eating syndrome or sleep related eating disorder. Night eating syndrome (NES is an eating disorder characterised by the clinical features of morning anorexia, evening hyperphagia, and insomnia with awakenings followed by nocturnal food ingestion. Recently night eating syndrome, conceptualized as a delayed circadian intake of food. Sleep-related eating disorder, thought to represent a parasomnia and as such included within the revised International Classification of Sleep Disorders (ICSD-2, and characterized by nocturnal partial arousals associated with recurrent episodes of involuntary food consumption and altered levels of consciousness. Whether, however, sleep-related eating disorder and night eating syndrome represent different diseases or are part of a continuum is still debated. This review summarizes their characteristics, treatment outcomes and differences between them.

  11. Theory of disordered superconductors

    International Nuclear Information System (INIS)

    Wysokinski, K.I.

    1991-01-01

    The influence of disorder on the superconducting transition temperature is discussed. The main steps on the way to complete theory of disordered superconductors follows the steps in the authors' understanding of disorder and its effect on the quasiparticles in metals. Loosely speaking one can distinguish three such steps. First is the study of weakly disordered systems and this resulted in famous, celebrated Anderson theorem. The second step is ultimately connected with the coherent potential approximation as a method to study the spectrum and transport in concentrated alloys. The discovery of the role of usually neglected interferences between scattered waves in disordered conductors leading to decrease in mobility and increase of the mutual interactions between quantum particles, known as localization and interaction effects has given the new impetus to the theory of superconductivity. This is third step to be discussed in this lecture. The authors limit themselves to homogeneous bulk superconductors. In this paper some experiments on thin films as well as on copper oxides related to the presented theory are briefly mentioned

  12. Bipolar Disorder in Children

    Science.gov (United States)

    2014-01-01

    Although bipolar disorder historically was thought to only occur rarely in children and adolescents, there has been a significant increase in children and adolescents who are receiving this diagnosis more recently (Carlson, 2005). Nonetheless, the applicability of the current bipolar disorder diagnostic criteria for children, particularly preschool children, remains unclear, even though much work has been focused on this area. As a result, more work needs to be done to further the understanding of bipolar symptoms in children. It is hoped that this paper can assist psychologists and other health service providers in gleaning a snapshot of the literature in this area so that they can gain an understanding of the diagnostic criteria and other behaviors that may be relevant and be informed about potential approaches for assessment and treatment with children who meet bipolar disorder criteria. First, the history of bipolar symptoms and current diagnostic criteria will be discussed. Next, assessment strategies that may prove helpful for identifying bipolar disorder will be discussed. Then, treatments that may have relevance to children and their families will be discussed. Finally, conclusions regarding work with children who may have a bipolar disorder diagnosis will be offered. PMID:24800202

  13. [Creativity and bipolar disorder].

    Science.gov (United States)

    Maçkalı, Zeynep; Gülöksüz, Sinan; Oral, Timuçin

    2014-01-01

    The relationship between creativity and bipolar disorder has been an intriguing topic since ancient times. Early studies focused on describing characteristics of creative people. From the last quarter of the twentieth century, researchers began to focus on the relationship between mood disorders and creativity. Initially, the studies were based on biographical texts and the obtained results indicated a relationship between these two concepts. The limitations of the retrospective studies led the researchers to develop systematic investigations into this area. The systematic studies that have focused on artistic creativity have examined both the prevalence of mood disorders and the creative process. In addition, a group of researchers addressed the relationship in terms of affective temperaments. Through the end of the 90's, the scope of creativity was widened and the notion of everyday creativity was proposed. The emergence of this notion led researchers to investigate the associations of the creative process in ordinary (non-artist) individuals. In this review, the descriptions of creativity and creative process are mentioned. Also, the creative process is addressed with regards to bipolar disorder. Then, the relationship between creativity and bipolar disorder are evaluated in terms of aforementioned studies (biographical, systematic, psychobiographical, affective temperaments). In addition, a new model, the "Shared Vulnerability Model" which was developed to explain the relationship between creativity and psychopathology is introduced. Finally, the methodological limitations and the suggestions for resolving these limitations are included.

  14. Psychosexual disorders and dermatologists

    Directory of Open Access Journals (Sweden)

    Tarun Narang

    2016-01-01

    Full Text Available Sexual problems that are psychological in origin, rather than physiological, are called psychosexual disorders. Multiple factors, such as general health of the patient, chronic illnesses, psychiatric/psychological disorders, and socio-cultural factors, alone or in combination can be attributed to the development of psychosexual dysfunctions. The symptoms of these disorders vary for each individual and differ with gender. These disorders may be categorized as sexual dysfunction, paraphilias, and gender identity disorders. Dermatologists are sometimes consulted for sexual dysfunctions in their routine practice by the patients visiting sexually transmitted infections (STI clinics because a majority of the patients believe that these problems are caused by dysfunctions in the sex organs, and because people are hesitant to go to sexuality clinics and psychiatrists for such problems. Sometimes these patients are referred from other specialties such as urology or gynecology; most often, we attempt to search for STIs or other dermatoses on the genitalia and refer them back. We often underestimate the prevalence of sexual concerns of the patients or feel uncomfortable discussing matters of sexuality with them. Dermatologists should understand basic sexual medicine and ask patients for sexual problems. They should be trained to manage such patients accordingly. In this review, we will be focusing on sexual dysfunctions, their etiopathogenesis, and management from a dermatologist's perspective.

  15. Psychosexual disorders and dermatologists

    Science.gov (United States)

    Narang, Tarun; Garima; Singh, Shubh M.

    2016-01-01

    Sexual problems that are psychological in origin, rather than physiological, are called psychosexual disorders. Multiple factors, such as general health of the patient, chronic illnesses, psychiatric/psychological disorders, and socio-cultural factors, alone or in combination can be attributed to the development of psychosexual dysfunctions. The symptoms of these disorders vary for each individual and differ with gender. These disorders may be categorized as sexual dysfunction, paraphilias, and gender identity disorders. Dermatologists are sometimes consulted for sexual dysfunctions in their routine practice by the patients visiting sexually transmitted infections (STI) clinics because a majority of the patients believe that these problems are caused by dysfunctions in the sex organs, and because people are hesitant to go to sexuality clinics and psychiatrists for such problems. Sometimes these patients are referred from other specialties such as urology or gynecology; most often, we attempt to search for STIs or other dermatoses on the genitalia and refer them back. We often underestimate the prevalence of sexual concerns of the patients or feel uncomfortable discussing matters of sexuality with them. Dermatologists should understand basic sexual medicine and ask patients for sexual problems. They should be trained to manage such patients accordingly. In this review, we will be focusing on sexual dysfunctions, their etiopathogenesis, and management from a dermatologist's perspective. PMID:27294047

  16. Esophageal motility disorders

    International Nuclear Information System (INIS)

    Hannig, C.; Rummeny, E.; Wuttge-Hannig, A.

    2007-01-01

    For the better understanding of esophageal motility, the muscle texture and the distribution of skeletal and smooth muscle fibers in the esophagus are of crucial importance. Esophageal physiology will be shortly mentioned as far as necessary for a comprehensive understanding of peristaltic disturbances. Besides the pure depiction of morphologic criteria, a complete esophageal study has to include an analysis of the motility. New diagnostic tools with reduced radiation for dynamic imaging (digital fluoroscopy, videofluoroscopy) at 4-30 frames/s are available. Radiomanometry is a combination of a functional pressure measurement and a simultaneous dynamic morphologic analysis. Esophageal motility disorders are subdivided by radiologic and manometric criteria into primary, secondary, and nonclassifiable forms. Primary motility disorders of the esophagus are achalasia, diffuse esophageal spasm, nutcracker esophagus, and the hypertonic lower esophageal sphincter. The secondary motility disorders include pseudoachalasia, reflux-associated motility disorders, functionally caused impactions, Boerhaave's syndrome, Chagas' disease, scleroderma, and presbyesophagus. The nonclassificable motility disorders (NEMD) are a very heterogeneous collective. (orig.) [de

  17. Taste disorders: A review

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Ambaldhage

    2014-01-01

    Full Text Available For maintenance of the health of an individual, taste sensation is very important. It is an important sensation that serves to assess the nutritious content of food, support oral intake, and prevent ingestion of potentially toxic substances. Disturbances in the perception of taste can lead to loss of appetite, causing malnutrition and thus distressing both the physical and psychological well-being of the patient. Oral physicians are often the first clinicians who hear complaints about alteration in taste from the patients. In spite of the effect of taste changes on health, literature on the diagnosis, pathogenesis, and precise treatment of taste disorders are less. Taste changes may lead patients to seek inappropriate dental treatments. Proper diagnosis of the etiology is the foremost step in the treatment of taste disorders. Thus, it is important that dental clinicians to be familiar with the various causes and proper management of taste changes. In this article, we have reviewed related articles focusing on taste disorders and their management, to provide a quick sketch for the clinicians. A detailed search was performed to identify the systematic reviews and research articles on taste disorders, using PUBMED and Cochrane. All the authors independently extracted data for analysis and review. Ultimately, 26 articles underwent a full text review. In conclusion, the research to date certainly offers us valid management strategies for taste disorders. Meanwhile, practical strategies with the highest success are needed for further intervention.

  18. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  19. Immunologic Endocrine Disorders

    Science.gov (United States)

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

  20. Differential diagnosis of bipolar disorder and major depressive disorder.

    Science.gov (United States)

    Hirschfeld, R M

    2014-12-01

    Patients with bipolar disorder spend approximately half of their lives symptomatic and the majority of that time suffering from symptoms of depression, which complicates the accurate diagnosis of bipolar disorder. Challenges in the differential diagnosis of bipolar disorder and major depressive disorder are reviewed, and the clinical utility of several screening instruments is evaluated. The estimated lifetime prevalence of major depressive disorder (i.e., unipolar depression) is over 3 and one-half times that of bipolar spectrum disorders. The clinical presentation of a major depressive episode in a bipolar disorder patient does not differ substantially from that of a patient with major depressive disorder (unipolar depression). Therefore, it is not surprising that without proper screening and comprehensive evaluation many patients with bipolar disorder may be misdiagnosed with major depressive disorder (unipolar depression). In general, antidepressants have demonstrated little or no efficacy for depressive episodes associated with bipolar disorder, and treatment guidelines recommend using antidepressants only as an adjunct to mood stabilizers for patients with bipolar disorder. Thus, correct identification of bipolar disorder among patients who present with depression is critical for providing appropriate treatment and improving patient outcomes. Clinical characteristics indicative of bipolar disorder versus major depressive disorder identified in this review are based on group differences and may not apply to each individual patient. The overview of demographic and clinical characteristics provided by this review may help medical professionals distinguish between major depressive disorder and bipolar disorder. Several validated, easily administered screening instruments are available and can greatly improve the recognition of bipolar disorder in patients with depression. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Congenital imprinting disorders

    DEFF Research Database (Denmark)

    Eggermann, Thomas; Netchine, Irène; Temple, I Karen

    2015-01-01

    Imprinting disorders (IDs) are a group of eight rare but probably underdiagnosed congenital diseases affecting growth, development and metabolism. They are caused by similar molecular changes affecting regulation, dosage or the genomic sequence of imprinted genes. Each ID is characterised...... by specific clinical features, and, as each appeared to be associated with specific imprinting defects, they have been widely regarded as separate entities. However, they share clinical characteristics and can show overlapping molecular alterations. Nevertheless, IDs are usually studied separately despite...... EUCID.net (European network of congenital imprinting disorders) now aims to promote better clinical care and scientific investigation of imprinting disorders by establishing a concerted multidisciplinary alliance of clinicians, researchers, patients and families. By encompassing all IDs and establishing...

  2. Delusion disorder: Neuropsychological aspects

    Directory of Open Access Journals (Sweden)

    Leposavić Ivana

    2004-01-01

    Full Text Available Previous studies concerned with neuropsychological aspect of delusions, were mainly focused on specific forms of this disorder. Comparatively small number of investigations were concerned with cognitive deficiencies accompanying the delusions. The substance of this study includes the detection of neuropsychological disfunctions in patients with persistent delusion disorder, and in tracing of these cognitive distortions to appropriate brain regions. Besides, characteristics of attribution style in these patients are analysed, from the aspect of their connections with unadjusted localized input for their reasoning system. The investigation is designed as a comparative study. The sample includes: a group of patients with persistent delusion disorder; a group of patients with paranoid schizophrenia; a group of healthy individuals. The participants have been tested by a neuropsychological battery that represents the following cognitive functions: attention, memory, vizuospatial and vizuoconstruction organization, executive ability, verbal divergent thinking. Projective Rorschach's method was used for estimation of attribution style.

  3. Premenstrual disorders and rumination.

    Science.gov (United States)

    Craner, Julia R; Sigmon, Sandra T; Martinson, Amber A; McGillicuddy, Morgan L

    2014-01-01

    Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) involve emotional, behavioral, and physical symptoms; however, there is little understanding of psychological factors that contribute to these disorders. It was hypothesized that rumination, a form of depressive self-focused attention, is related to premenstrual distress. Study 1 involved women (N = 735) meeting criteria for No/Mild PMS, Moderate/Severe PMS, and PMDD using retrospective self-report. Study 2 involved women (N = 85) meeting diagnostic criteria for PMS or PMDD (i.e., PMD group) and healthy controls (i.e., No PMD group) following 60-day symptom monitoring. Participants in both studies completed questionnaires of rumination, anxiety sensitivity, and coping styles. Rumination was strongly related to premenstrual disorders using both retrospective and prospective reports, as well as both categorical and continuous approaches to classification of premenstrual distress. Rumination, a transdiagnostic factor in psychopathology, may contribute to the onset and maintenance of premenstrual distress. © 2013 Wiley Periodicals, Inc.

  4. [Bipolar disorder in adolescence].

    Science.gov (United States)

    Brunelle, Julie; Milhet, Vanessa; Consoli, Angèle; Cohen, David

    2014-04-01

    Juvenile mania is a concept widely developed but also highly debated since the 1990s. In the heart of this debate, Severe Mood Dysregulation (SMD) and "Temper Dysregulation disorder with Dysphoria" (recently integrated in DSM-5) showed their interest. Actually, the objective is to distinguish two clinical phenotypes in order to avoid confusion between (1) what would raise more of mood dysregulation with chronic manic like symptoms, and (2) bipolar disorder type I with episodic and acute manic episodes. Therapeutic stakes are major. In adolescents, even if DSM adult diagnostic criteria can be used and bipolar disorder type I clearly established, differential diagnostic at onset between acute manic episode and schizophrenia onset remain sometimes difficult to assess. Furthermore, it is crucial to better assess outcome of these adolescents, in terms of morbidity and potential prognosis factors, knowing that a younger age at onset is associated with a poorer outcome according to several adult studies. Therapeutic implications could then be drawn.

  5. [Cannabis-induced disorders].

    Science.gov (United States)

    Soyka, M; Preuss, U; Hoch, E

    2017-03-01

    Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

  6. Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    G Grobler

    2013-08-01

    Full Text Available The treatment guideline draws on several international guidelines: (iPractice Guidelines of the American Psychiatric Association (APAfor the Treatment of Patients with Major Depressive Disorder, SecondEdition;[1](ii Clinical Guidelines for the Treatment of DepressiveDisorders by the Canadian Psychiatric Association and the CanadianNetwork for Mood and Anxiety Treatments (CANMAT;[2](iiiNational Institute for Clinical Excellence (NICE guidelines;[3](iv RoyalAustralian and New Zealand College of Psychiatrists Clinical PracticeGuidelines Team for Depression (RANZCAP;[4](v Texas MedicationAlgorithm Project (TMAP Guidelines;[5](vi World Federation ofSocieties of Biological Psychiatry (WFSBP Treatment Guideline forUnipolar Depressive Disorder;[6]and (vii British Association forPsychopharmacology Guidelines.[7

  7. Medical comorbidity of sleep disorders.

    Science.gov (United States)

    Dikeos, Dimitris; Georgantopoulos, Georgios

    2011-07-01

    Recently published literature indicates that sleep disorders present with medical comorbidities quite frequently. The coexistence of a sleep disorder with a medical disorder has a substantial impact for both the patient and the health system. Insomnia and hypersomnia are highly comorbid with medical conditions, such as chronic pain and diabetes, as well as with various cardiovascular, respiratory, gastrointestinal, urinary and neurological disorders. Restless legs syndrome and periodic leg movement syndrome have been associated with iron deficiency, kidney disease, diabetes, and neurological, autoimmune, cardiovascular and respiratory disorders. Rapid eye movement behaviour disorder has been described as an early manifestation of serious central nervous system diseases; thus, close neurological monitoring of patients referring with this complaint is indicated. Identification and management of any sleep disorder in medical patients is important for optimizing the course and prognosis. Of equal importance is the search for undetected medical disorder in patients presenting with sleep disorders.

  8. Tic disorders and Tourette's syndrome

    DEFF Research Database (Denmark)

    Plessen, Kerstin J

    2012-01-01

    Diagnostic categories of tic disorders include both transient and chronic tic disorders and Tourette's disorder. Changes for this group of disorders proposed for the forthcoming DSM-5 system include: (1) The term "stereotyped" will be eliminated in the definition of tics and the new definition...... will be applied consistently across all entities of tic disorders; (2) the diagnosis "Transient Tic Disorder" will change its name to "Provisional Tic Disorder"; (3) introduction of two new categories in individuals whose tics are triggered by illicit drugs or by a medical condition; (4) specification of chronic...... tic disorders into those with motor tics or with vocal tics only; (5) specification of the absence of a period longer than 3 months without tics will disappear for Tourette's Disorder. This overview discusses a number of implications resulting from these diagnostic modifications of the diagnostic...

  9. Childhood disintegrative disorder

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik

    2003-01-01

    In 1908 a Viennese remedial educator Theodor Heller described six children under the name of dementia infantilis who had insidiously developed a severe mental regression between the 3rd and 4th years of life after normal mental development. Neuropathological and other medical conditions...... are sometimes associated with this disorder, but contrary to earlier belief this is not typical. Interest in childhood disintegrative disorder has increased markedly in recent years and in this review attention is given to more recently published cases based on ICD-9, ICD-10 and DSM-IV diagnostic systems...

  10. Stereotypic movement disorders.

    Science.gov (United States)

    Singer, Harvey S

    2011-01-01

    Stereotypic movements are repetitive, rhythmic, fixed, patterned in form, amplitude, and localization, but purposeless (e.g., hand shaking, waving, body rocking, head nodding). They are commonly seen in children; both in normal children (primary stereotypy) and in individuals with additional behavioral or neurological signs and symptoms (secondary stereotypy). They should be differentiated from compulsions (OCD), tics (tic disorders), trichotillomania, skin picking disorder, or the direct physiological effect of a substance. There is increasing evidence to support a neurobiological mechanism. Response to behavioral and pharmacological therapies is variable. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Female reproductive disorders

    DEFF Research Database (Denmark)

    Crain, D Andrew; Janssen, Sarah J; Edwards, Thea M

    2008-01-01

    To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disrupti......To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive...... disruptions warrant evaluation of the impact of EDCs on female reproductive health....

  12. Extrapyramidal disorders in childhood

    International Nuclear Information System (INIS)

    Angelini, L.; Nardocci, N.; Balottin, U.; Lanzi, G.

    1987-01-01

    Movement disorders have become significantly interesting as a subject in the Neurosciences. The majority of the data, however, relate to the more specific problems of extrapyramidal disorders in adults. As a disease in childhood it still remains poorly systemized. This book is a collection of certain studies with reference to the most recent advances regarding the morphofunctional organization of the basal ganglia in relation to development. Moreover, the book attempts to systemize the extrapyramidal diseases typical of childhood or at the onset in childhood, focusing on diagnostic and therapeutic criteria. refs.; figs.; tabs

  13. [Prevention of mental disorders].

    Science.gov (United States)

    Riedel-Heller, Steffi; Gühne, Uta

    2013-12-01

    Investment in prevention is a major public health requirement. Mental disorders are common and are associated with severe consequences. They are a major target for prevention. Based on vulnerabilitiy-stress-models the theoretical background for prevention in mental disorders is outlined. Effective strategies for children, adolescents, adults and individuals in old age do exist. Results regarding the prevention of depres-sion and psychoses are outlined and risk groups which require current actions are determined. Current activities towards a national prevention strategy in Germany are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Nonuniversal disordered Glauber dynamics.

    Science.gov (United States)

    Grynberg, Marcelo D; Stinchcombe, Robin B

    2013-06-01

    We consider the one-dimensional Glauber dynamics with coupling disorder in terms of bilinear fermion Hamiltonians. Dynamic exponents embodied in the spectrum gap of these latter are evaluated numerically by averaging over both binary and Gaussian disorder realizations. In the first case, these exponents are found to follow the nonuniversal values of those of plain dimerized chains. In the second situation their values are still nonuniversal and subdiffusive below a critical variance above which, however, the relaxation time is suggested to grow as a stretched exponential of the equilibrium correlation length.

  15. [Narcissistic personality disorder].

    Science.gov (United States)

    Lammers, C-H; Vater, A; Roepke, S

    2013-07-01

    Narcissism is a multifaceted term which encompasses traits of normal personality as well as a specific personality disorder. While much research has been concerned with narcissism as a trait there are only few empirical studies available on narcissistic personality disorder (NPS). The current diagnostic of NPS according to DSM-IV-TR focuses on grandiose type narcissism whereas vulnerable narcissism, which has been described by clinicians and researchers has not yet been recognised. Psychotherapy of narcissistic patients through different psychotherapeutic schools focuses mainly on processes in the therapeutic relationship, the analysis and change of grandiose and vulnerable schemas, emotion regulation techniques and correction of narcissistic behavior in favor of prosocial interactions.

  16. Sleep Disturbances in Mood Disorders.

    Science.gov (United States)

    Rumble, Meredith E; White, Kaitlin Hanley; Benca, Ruth M

    2015-12-01

    The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Child development and personality disorder.

    Science.gov (United States)

    Cohen, Patricia

    2008-09-01

    The evidence is surprisingly strong that even early adolescent personality disorders or elevated personality disorder symptoms have a broad range of negative effects well into adulthood, for the most part comparable to or even larger than those of Axis I disorders. Current evidence suggests that the most severe long-term prognosis is associated with borderline and schizotypal PDs and elevated symptoms. And of course, childhood conduct disorder is in a peculiar status, disappearing in adulthood to be manifest as a very severe disorder-antisocial PD-in a minority of those with the adolescent disorder.

  18. Random walk in dynamically disordered chains: Poisson white noise disorder

    International Nuclear Information System (INIS)

    Hernandez-Garcia, E.; Pesquera, L.; Rodriguez, M.A.; San Miguel, M.

    1989-01-01

    Exact solutions are given for a variety of models of random walks in a chain with time-dependent disorder. Dynamic disorder is modeled by white Poisson noise. Models with site-independent (global) and site-dependent (local) disorder are considered. Results are described in terms of an affective random walk in a nondisordered medium. In the cases of global disorder the effective random walk contains multistep transitions, so that the continuous limit is not a diffusion process. In the cases of local disorder the effective process is equivalent to usual random walk in the absence of disorder but with slower diffusion. Difficulties associated with the continuous-limit representation of random walk in a disordered chain are discussed. In particular, the authors consider explicit cases in which taking the continuous limit and averaging over disorder sources do not commute

  19. Comparative Prevalence of Eating Disorders in Obsessive-Compulsive Disorder and Other Anxiety Disorders

    Directory of Open Access Journals (Sweden)

    Himanshu Tyagi

    2015-01-01

    Full Text Available Objective. The purpose of this study was to compare the prevalence of comorbid eating disorders in Obsessive-Compulsive Disorder (OCD and other common anxiety disorders. Method. 179 patients from the same geographical area with a diagnosis of OCD or an anxiety disorder were divided into two groups based on their primary diagnosis. The prevalence of a comorbid eating disorder was calculated in both groups. Results. There was no statistically significant difference in the prevalence of comorbid eating disorders between the OCD and other anxiety disorders group. Conclusions. These results suggest that the prevalence of comorbid eating disorders does not differ in anxiety disorders when compared with OCD. However, in both groups, it remains statistically higher than that of the general population.

  20. Health Anxiety in Panic Disorder, Somatization Disorder and Hypochondriasis

    OpenAIRE

    Özgün Karaer KARAPIÇAK; Selçuk ASLAN; Çisem UTKU

    2012-01-01

    Objective: Health anxiety is the fear of being or getting seriously sick due to the misinterpretation of physical symptoms. Severe health anxiety is also named as hypochondriasis. Belief of having a disease due to the misinterpretation of physical symptoms is also seen in panic disorder and somatization disorder. The aim of this study is to search the health anxiety in panic disorder, somatization disorder and hypochondriasis and compare it with healthy volunteers. Method: SCID-I was used ...

  1. Attention-deficit hyperactivity disorder in bipolar disorder

    OpenAIRE

    Rydén, Eleonore

    2010-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a developmental disorder, i.e., it is by definition present from childhood. The main features characterizing ADHD are the difficulties to regulate attention, activity level, and impulses. The hallmark of bipolar disorder is episodic mood alterations with restitution between episodes. Although debut in childhood may occur, bipolar disorder typically debuts in late adolescence or early adulthood. The overarching aim with this ...

  2. Binge eating disorder

    DEFF Research Database (Denmark)

    Schousboe, Birgitte Hartvig; Waaddegaard, Mette

    2011-01-01

    Binge eating disorder kaldes også bulimi uden opkastning eller den tredje spiseforstyrrelse. Det er en udbredt, men mindre kendt spiseforstyrrelse end anoreksi og bulimi. Patienterne er ofte overvægtige og har ikke kompenserende adfærd over for overspisningen i form af opkastning eller brug af...

  3. Persistent genital arousal disorder

    DEFF Research Database (Denmark)

    Eibye, Simone; Jensen, Hans Mørch

    2014-01-01

    We report a case of a woman suffering from persistent genital arousal disorder (PGAD) after paroxetine cessation. She was admitted to a psychiatric department and diagnosed with agitated depression. Physical investigation showed no gynaecological or neurological explanation; however, a pelvic MRI...

  4. Strongly disordered superconductors

    International Nuclear Information System (INIS)

    Muttalib, K.A.

    1982-01-01

    We examine some universal effects of strong non-magnetic disorder on the electron-phonon and electron-electron interactions in a superconductor. In particular we explicitly take into account the effect of slow diffusion of electrons in a disordered medium by working in an exact impurity eigenstate representation. We find that the normal diffusion of electrons characterized by a constant diffusion coefficient does not lead to any significant correction to the electron-phonon or the effective electron-electron interactions in a superconductor. We then consider sufficiently strong disorder where Anderson localization of electrons becomes important and determine the effect of localization on the electron-electron interactions. We find that due to localization, the diffusion of electrons becomes anomalous in the sense that the diffusion coefficient becomes scale dependent. This results in an increase in the effective electron-electron interaction with increasing disorder. We propose that this provides a natural explanation for the unusual sensitivity of the transition temperature T/sub c/ of the high T/sub c/ superconductors (T/sub c/ > 10 0 K) to damage effects

  5. Types of Bipolar Disorder

    Science.gov (United States)

    ... Events Home Science News Meetings and Events Multimedia Social Media Press Resources Newsletters NIMH News Feeds About Us ... has a lot of money, or has special powers. Someone having psychotic symptoms ... Substance Abuse: People with bipolar disorder may also misuse alcohol ...

  6. Disordered chaotic strings

    DEFF Research Database (Denmark)

    Schäfer, Mirko; Greiner, Martin

    2011-01-01

    to chaotic strings. Inhomogeneous coupling weights as well as small-world perturbations of the ring-network structure are discussed. It is found that certain combinations of coupling and network disorder preserve the empirical relationship between chaotic strings and the weak and strong sector...

  7. Autism Spectrum Disorder

    Centers for Disease Control (CDC) Podcasts

    2014-04-02

    This podcast discusses autism spectrum disorder (ASD), a developmental disability that causes problems with social, communication, and behavioral skills. CDC estimates that one in 68 children has been identified as having ASD.  Created: 4/2/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 4/2/2014.

  8. Wikipedia and neurological disorders

    NARCIS (Netherlands)

    Brigo, Francesco; Igwe, Stanley C.; Nardone, Raffaele; Lochner, Piergiorgio; Tezzon, Frediano; Otte, WM

    2015-01-01

    Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a

  9. Treatments for Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Di Pietro, Nina C; Whiteley, Louise Emma; Mizgalewicz, Ania

    2013-01-01

    The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly...

  10. Exporting Our Disorders

    Science.gov (United States)

    Foltz, Robert

    2012-01-01

    In 2013, the American Psychiatric Association will release its newest Diagnostic and Statistical Manual, 5th Edition (DSM-5). This tome has evolved over the decades, originally including just 112 diagnoses across 128 pages. The upcoming edition is expected to eclipse the 943 pages, and 350+ disorders of the current DSM-IV-TR, offering a variety of…

  11. Adjustment disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Zelviene P

    2018-01-01

    Full Text Available Paulina Zelviene, Evaldas Kazlauskas Department of Clinical and Organizational Psychology, Vilnius University, Vilnius, Lithuania Abstract: Adjustment disorder (AjD is among the most often diagnosed mental disorders in clinical practice. This paper reviews current status of AjD research and discusses scientific and clinical issues associated with AjD. AjD has been included in diagnostic classifications for over 50 years. Still, the diagnostic criteria for AjD remain vague and cause difficulties to mental health professionals. Controversies in definition resulted in the lack of reliable and valid measures of AjD. Epidemiological data on prevalence of AjD is scarce and not reliable because prevalence data are biased by the diagnostic algorithm, which is usually developed for each study, as no established diagnostic standards for AjD are available. Considerable changes in the field of AjD could follow after the release of the 11th edition of International Classification of Diseases (ICD-11. A new AjD symptom profile was introduced in ICD-11 with 2 main symptoms as follows: 1 preoccupation and 2 failure to adapt. However, differences between the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and ICD-11 AjD diagnostic criteria could result in diverse research findings in the future. The best treatment approach for AjD remains unclear, and further treatment studies are needed to provide AjD treatment guidelines to clinicians. Keywords: adjustment disorder, review, diagnosis, prevalence, treatment, DSM, ICD

  12. Studies of Personality Disorders

    DEFF Research Database (Denmark)

    Ronningstam, Elsa; Simonsen, Erik; Oldham, John M

    2014-01-01

    The past 25 years have shown major advances in the studies of personality disorders. This collaborative article by the presidents, past and present, of ISSPD reflects on the progress within several significant areas of studies, i.e., assessment, neuroscience, treatment, prevention, advocacy...

  13. Personality and psychotic disorders

    NARCIS (Netherlands)

    Boyette, L.L.N.J.

    2014-01-01

    The subject of the current thesis is the contribution of normal personality traits as conceptualized by the Five-Factor Model of personality (FFM) to the manifestation of illness in patients with psychotic disorders. These studies were part of the Dutch national Genetic Risk and Outcome of Psychosis

  14. Coping with disorder

    DEFF Research Database (Denmark)

    Mosebo, Marianne Bach

    2008-01-01

    The traditionally pastoral people of Karamoja live in an environment fraught with violence, poverty and disorder. However, they also just live life. In this article, I speak out against an imbalance, which I claim exists in the literature on Karamoja; namely that it focuses primarily on the negat...

  15. Functional Anorectal Disorders.

    Science.gov (United States)

    Rao, Satish Sc; Bharucha, Adil E; Chiarioni, Giuseppe; Felt-Bersma, Richelle; Knowles, Charles; Malcolm, Allison; Wald, Arnold

    2016-03-25

    This report defines criteria and reviews the epidemiology, pathophysiology, and management of common anorectal disorders: fecal incontinence (FI), functional anorectal pain and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into three subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome (LAS) and unspecified anorectal pain the pain lasts more than 30 minutes, but in LAS there is puborectalis tenderness. Functional defecation disorders are defined by >2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with >2 features of impaired evacuation i.e., abnormal evacuation pattern on manometry, abnormal balloon expulsion test or impaired rectal evacuation by imaging. It includes two subtypes; dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating LAS and defecatory disorders. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Nutritional disorders in chrysanthemums

    NARCIS (Netherlands)

    Roorda van Eysinga, J.P.N.L.; Smilde, K.W.

    1980-01-01

    This book is a guide to diagnosing nutritional disorders in chrysanthemums. Deficiencies and toxicities are included, fifteen in all. Colour plates and descriptions are given for nitrogen, phosphorus, potassium, magnesium, calcium, sulphur, boron, copper, manganese, iron and zinc deficiency and for

  17. Pharmacotherapy of eating disorders.

    Science.gov (United States)

    Davis, Haley; Attia, Evelyn

    2017-11-01

    Medications are commonly prescribed in the treatment of eating disorders. In this review, we discuss relevant medications used for the treatment of bulimia nervosa, binge eating disorder (BED), and anorexia nervosa. We focus on recent research developments, where applicable, in addition to discussing important findings from older studies to provide a complete synopsis of the current evidence base for eating disorder treatment using pharmacologic agents. Medications are generally useful for patients with bulimia nervosa and BED. For bulimia nervosa, antidepressant medications are the primary pharmacologic treatment and limited new research has been completed. For BED, lisdexamfetamine is reported to be generally well tolerated and effective, and is the first medication to be indicated by the US Food and Drug Administration for treatment of BED. For anorexia nervosa, there is limited evidence supporting benefits of medications. Second-generation antipsychotics, particularly olanzapine, appear to demonstrate some benefit for weight gain in anorexia nervosa, although are not advised as a stand-alone treatment. Transdermal administration of hormonal agents is also being explored for improving bone health in anorexia nervosa. Although pharmacotherapy has established utility in bulimia nervosa and BED, further research on medications for the treatment of eating disorders, particularly anorexia nervosa, is necessary.

  18. Women's Sexual Pain Disorders

    NARCIS (Netherlands)

    van Lankveld, Jacques J. D. M.; Granot, Michal; Schultz, Willibrord C. M. Weijmar; Binik, Yitzchak M.; Wesselmann, Ursula; Pukall, Caroline F.; Bohm-Starke, Nina; Achtrari, Chahin

    Introduction. Women's sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area. Aim. To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and

  19. Dwarf Eye Disorder

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Johns Hopkins researchers at the Wilmer Eye Institute have discovered what appears to be the first human gene mutation that causes extreme farsightedness. The researchers report that nanophthalmos, Greek for "dwarf eye," is a rare, potentially blinding disorder caused by an alteration in a gene called MFRP that helps control eye growth and…

  20. Whiplash-Associated Disorders

    DEFF Research Database (Denmark)

    Ferrara, S. D.; Ananian, V.; Baccino, E.

    2016-01-01

    The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD). The document...

  1. Bipolar Disorder and Cancer

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2012-06-01

    Full Text Available Prevalence studies and studies on causation relations have shown that the relation between psychiatric disorders and chronic physical diseases is neglected. For heterogeneous diseases an increasing number of susceptibility variants are being defined. Alzheimer disease, bipolar disorder, breast and prostate cancer, coronary artery disease, Chron's disease, systemic lupus eritematosus, type 1 and type 2 diabetes mellitus are mentioned together with epigenetic concept. In acrocentric zone of chromosome 13, breast cancer, retinoblastoma, chronic Iymphocytic leukemia genes with B cells, dopamin loci of bipolar disorder are found together. Among bipolar and healthy individuals, an increase risk of breast cancer in female cases has been resported. On the other hand, psychosocial factors that affect stress and response to stress itself may be important variables in prognosis and progression of different cancer types. During the course of many cancer types –especially brain tumors- and during treatment of chemotherapeutic agents, bipolar symptomatology may appear. In this article, it is reviewed with relevant literature that whether an etiological relation between bipolar disorder and cancer exist and how both diseases affect each other's course and treatment.

  2. Body Integrity Identity Disorder

    NARCIS (Netherlands)

    Blom, Rianne M.; Hennekam, Raoul C.; Denys, Damiaan

    2012-01-01

    Introduction: Body Integrity Identity Disorder (BIID) is a rare, infrequently studied and highly secretive condition in which there is a mismatch between the mental body image and the physical body. Subjects suffering from BIID have an intense desire to amputate a major limb or severe the spinal

  3. Auditory Processing Disorders

    Science.gov (United States)

    ... many processes and problems contribute to APD in children. In adults, neurological disorders such as stroke, tumors, degenerative disease (such as multiple sclerosis), and head trauma can contribute to APD. APD in children and adults often is best managed by a ...

  4. Body dysmorphic disorder

    DEFF Research Database (Denmark)

    Jawad, Mustafa Bashir M; Sjögren, Magnus

    2017-01-01

    Body dysmorphic disorder is defined by a preoccupation of one or more non-existent or slight defects or flaws in the physical appearance. The prevalence is 1.7-2.4% in the general population with a higher incidence rate in women. The rate of suicidal ideation is as high as 80%, and up to 25...

  5. Borderline Personality Disorder

    Science.gov (United States)

    ... of a mood disorder—not borderline personality disorder Self-harming behavior, such as cutting Recurring thoughts of suicidal ... symptoms and reduce the number of suicidal or self-harming behaviors. Read more on NIMH’s Psychotherapies health topic ...

  6. Fatty Acid Oxidation Disorders

    Science.gov (United States)

    ... of VLCAD, symptoms appear closer to a baby’s first birthday or in early childhood. About one-third of all people with VLCAD have childhood VLCAD. Adult VLCAD . About 20 percent of with VLCAD have ... Some of these disorders can first appear in adults, but this is rare. Illness ...

  7. Female reproductive disorders

    DEFF Research Database (Denmark)

    Crain, D Andrew; Janssen, Sarah J; Edwards, Thea M

    2008-01-01

    To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive...... disruptions warrant evaluation of the impact of EDCs on female reproductive health....

  8. [Complex posttraumatic stress disorder].

    Science.gov (United States)

    Green, Tamar; Kotler, Moshe

    2007-11-01

    The characteristic symptoms resulting from exposure to an extreme trauma include three clusters of symptoms: persistent experience of the traumatic event, persistent avoidance of stimuli associated with the trauma and persistent symptoms of increased arousal. Beyond the accepted clusters of symptoms for posttraumatic stress disorder exists a formation of symptoms related to exposure to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and confinement within a concentration camp. With accumulated evidence of the existence of these symptoms began a trail to classify a more complex syndrome, which included, but was not confined to the symptoms of posttraumatic stress disorder. This review addresses several subjects for study in complex posttraumatic stress disorder, which is a complicated and controversial topic. Firstly, the concept of complex posttraumatic stress disorder is presented. Secondly, the professional literature relevant to this disturbance is reviewed and finally, the authors present the polemic being conducted between the researchers of posttraumatic disturbances regarding validity, reliability and the need for separate diagnosis for these symptoms.

  9. Wikipedia and neurological disorders.

    Science.gov (United States)

    Brigo, Francesco; Igwe, Stanley C; Nardone, Raffaele; Lochner, Piergiorgio; Tezzon, Frediano; Otte, Willem M

    2015-07-01

    Our aim was to evaluate Wikipedia page visits in relation to the most common neurological disorders by determining which factors are related to peaks in Wikipedia searches for these conditions. Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopedia used by patients and physicians to search for health-related information. The following Wikipedia articles were considered: Alzheimer's disease; Amyotrophic lateral sclerosis; Dementia; Epilepsy; Epileptic seizure; Migraine; Multiple sclerosis; Parkinson's disease; Stroke; Traumatic brain injury. We analyzed information regarding the total article views for 90 days and the rank of these articles among all those available in Wikipedia. We determined the highest search volume peaks to identify possible relation with online news headlines. No relation between incidence or prevalence of neurological disorders and the search volume for the related articles was found. Seven out of 10 neurological conditions showed relations in search volume peaks and news headlines. Six out of these seven peaks were related to news about famous people suffering from neurological disorders, especially those from showbusiness. Identification of discrepancies between disease burden and health seeking behavior on Wikipedia is useful in the planning of public health campaigns. Celebrities who publicly announce their neurological diagnosis might effectively promote awareness programs, increase public knowledge and reduce stigma related to diagnoses of neurological disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Mood disorder history and personality assessment in premenstrual dysphoric disorder.

    Science.gov (United States)

    Critchlow, D G; Bond, A J; Wingrove, J

    2001-09-01

    Menstrually related dysphoria is known to be associated with other affective disorders, notably major depressive disorder and puerperal depression. The relationship between premenstrual dysphoric disorder (PMDD) and maladaptive personality disorders and traits, however, is less established, at least in part because of the methodological and nosologic difficulties in the diagnosis of both PMDD and personality disorders. This study seeks to address this problem to elucidate the relationship between PMDD, other affective disturbances commonly experienced by women, and maladaptive personality. Axis I and II disorders were examined using standardized instruments and stringent diagnostic criteria (DSM-IV and the International Personality Disorders Examination) in 34 women with DSM-IV PMDD and 22 healthy women without severe premenstrual mood changes. Seventy-seven percent of the PMDD group had suffered from a past Axis I disorder in comparison with 17% of the control group. Two thirds of the parous women with PMDD had suffered from major depressive disorder in the puerperium. Personality disorder diagnoses were not highly represented in either group of women. The women with PMDD had significantly more obsessional personality traits (p personality disorder diagnoses. Obsessional symptoms are known to cluster with the affective disorders and may reflect underlying temperamental and biological vulnerability. This study provides further evidence of the link between serotonergic dysregulation, personality vulnerability, and mood changes related to the female reproductive cycle.

  11. Difference or Disorder? Cultural Issues in Understanding Neurodevelopmental Disorders

    Science.gov (United States)

    Norbury, Courtenay Frazier; Sparks, Alison

    2013-01-01

    Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality…

  12. Post-traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    S Seedat

    2013-08-01

    Full Text Available Post-traumatic stress disorder (PTSD is among the most prevalentanxiety disorders, both in terms of lifetime and 12-month prevalencerates documented in epidemiological studies worldwide.

  13. Eating disorders in college men.

    Science.gov (United States)

    Olivardia, R; Pope, H G; Mangweth, B; Hudson, J I

    1995-09-01

    This study was designed to assess the characteristics of men with eating disorders in the community. The authors recruited 25 men meeting DSM-IV criteria for eating disorders and 25 comparison men through advertisements in college newspapers. A second comparison group comprised 33 women with bulimia nervosa who were recruited and interviewed with virtually identical methods. The men with eating disorders closely resembled the women with eating disorders but differed sharply from the comparison men in phenomenology of illness, rates of comorbid psychiatric disorders, and dissatisfaction with body image. Homosexuality did not appear to be a common feature of men with eating disorders in the community. Childhood physical and sexual abuse appeared slightly more common among the eating-disordered men than among the comparison men. Eating disorders, although less common in men than in women, appear to display strikingly similar features in affected individuals of the two genders.

  14. Somatic Symptom and Related Disorders

    Science.gov (United States)

    ... A headache may mean a brain tumor. Body dysmorphic disorder occurs when a person becomes obsessed with ... body. Common concerns for people who have body dysmorphic disorder include: wrinkles hair loss weight gain size ...

  15. Sleep disorders in the elderly

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000064.htm Sleep disorders in older adults To use the sharing features on this page, please enable JavaScript. Sleep disorders in older adults involve any disrupted sleep ...

  16. Normal Stress or Adjustment Disorder?

    Science.gov (United States)

    ... disorder is a type of stress-related mental illness that can affect your feelings, thoughts and behaviors. Signs and symptoms of an adjustment disorder can include: Anxiety Poor school or work performance Relationship problems Sadness ...

  17. Attention deficit hyperactivity disorder (ADHD)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001551.htm Attention deficit hyperactivity disorder To use the sharing features on this page, please enable JavaScript. Attention deficit hyperactivity disorder (ADHD) is a problem caused by ...

  18. Obsessive Compulsive Disorder among Adults

    Science.gov (United States)

    ... Adults Data Sources Share Obsessive-Compulsive Disorder (OCD) Definition Obsessive-compulsive disorder (OCD) is often a long- ... MSC 9663 Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS ...

  19. [Basic disorders in human communication].

    Science.gov (United States)

    Peñaloza-López, Y; Gutiérrez-Silva, J; Andrade-Illañez, E N; Fierro-Evans, M A; Hernández-López, X

    1989-01-01

    This paper specifies the areas and disorders that concern human communication medicine. The frequency of the diverse disorders is analyzed in relation to age and sex, and the distribution in group ages of several disabling diseases is also discussed.

  20. Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns

    NARCIS (Netherlands)

    van Iterson, L.; de Jong, P.F.; Zijlstra, B.J.H.

    2015-01-01

    Introduction: In pediatric epilepsy, comorbidities are reported to be frequent. The present study focusedon the cognitive patterns of children with isolated epilepsy, children with isolated neurodevelopmental disorders (reading disorders, math disorders, autism spectrum disorders), and children with

  1. [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

    NARCIS (Netherlands)

    Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

    2006-01-01

    The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

  2. Temporomandibular disorders and migraine headache

    OpenAIRE

    Demarin, Vida; Bašić Kes, Vanja

    2010-01-01

    Migraine headache and temporomandibular disorders show significant overlap in the area or distribution of pain, the gender prevalence and age distribution. Temporomandibular disorders may cause headaches per se, worsen existent primary headaches, and add to the burden of headache disorders. The patients with combined migraine and tension-type headaches had a higher prevelance of temporomandibular disorders. Evidence supporting a close relationship include the increased masticatory...

  3. Comorbid personality disorders in subjects with panic disorder: which personality disorders increase clinical severity?

    Directory of Open Access Journals (Sweden)

    Mustafa Ozkan

    2003-03-01

    Full Text Available Personality disorders are common in subjects with panic disorder. Personality disorders have shown to affect the course of panic disorder. The purpose of this study was to examine which personality disorders effect clinical severity in subjects with panic disorder. This study included 122 adults (71 female, 41 male, who met DSM-IV criteria for panic disorder (with or without agoraphobia. Clinical assessment was conducted by using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II and the Panic and Agoraphobia Scale (PAS, Global Assessment Functioning Scale (GAF, Beck Depression Inventory (BDI, and State-Trait Anxiety Inventory (STAI. Patients who had a history of sexual abuse were assessed with Sexual Abuse Severity Scale. Logistic regressions were used to identify predictors of suicide attempts, suicidal ideation, agoraphobia, different panic attack symptoms, sexual abuse, and early onset of disorders. The rates of comorbid Axis I and Axis II psychiatric disorders were 80.3% and 33.9%, consecutively, in patients with panic disorder. Panic disorder patients with comorbid personality disorders had more severe anxiety, depression and agoraphobia symptoms, and had earlier ages of onset, and lower levels of functioning. The rates of suicidal ideation and suicide attempts were 34.8% and 9.8%, consecutively, in subjects with panic disorder. The rate of patients with panic disorder had a history of childhood sexual abuse was 12.5%. The predictor of sexual abuse was more than one comorbid Axis II diagnosis. The predictors of suicide attempt were comorbid paranoid and borderline personality disorders, and the predictor of suicidal ideation was major depressive disorder in subjects with panic disorder. In conclusion, this study documents that comorbid personality disorders increase the clinical severity of panic disorder. Patients with more than one

  4. Cultural trends and eating disorders

    NARCIS (Netherlands)

    Pike, Kathleen M.; Hoek, Hans W.; Dunne, Patricia E.

    2014-01-01

    Purpose of review Culture has long been recognized as significant to the cause and expression of eating disorders. We reviewed the recent literature about recent trends in the occurrence of eating disorders in different cultures. Recent findings While historically, eating disorders were

  5. Narcissism and Narcissistic Personality Disorder

    Directory of Open Access Journals (Sweden)

    Gerhard Dammann

    2017-04-01

    Full Text Available This a video is one of the series of lectures about personality disorders. It covers the concept of narcissism and the concept of narcissism personality disorder.  The lecture is mainly focused on the differences between normal and pathological narcissism as well as etiology, diagnosis and practical recommendations on treatment of narcissism personality disorder.

  6. Cultural trends and eating disorders

    NARCIS (Netherlands)

    Pike, Kathleen M.; Hoek, Hans W.; Dunne, Patricia E.

    Purpose of review Culture has long been recognized as significant to the cause and expression of eating disorders. We reviewed the recent literature about recent trends in the occurrence of eating disorders in different cultures. Recent findings While historically, eating disorders were

  7. Eating Disorders in Paraguayan Adolescents

    Science.gov (United States)

    Ramirez, Maria E.; McIntosh, David E.; Kruczek, Theresa

    2013-01-01

    Eating disorders, once thought to be exclusively a disorder of the more affluent Western countries, are now spreading around the world. Despite the wealth of information on the prevalence of eating disorders in developed countries, epidemiological data for South America is scarce. The 26-item Eating Attitude Test (EAT-26) was used to explore the…

  8. [Autism spectrum disorders in adults

    NARCIS (Netherlands)

    Kan, C.C.; Buitelaar, J.K.; Gaag, R.J. van der

    2008-01-01

    Early infantile autism' as defined by Kanner has grown into a spectrum of autistic disorders. The recognition of Asperger's disorder and of pervasive developmental disorder not otherwise specified (PDD-NOS), has led to increased demand for appropriate diagnostic assessment of autism in adults. The

  9. Narcissism and Narcissistic Personality Disorder

    OpenAIRE

    Gerhard Dammann

    2017-01-01

    This a video is one of the series of lectures about personality disorders. It covers the concept of narcissism and the concept of narcissism personality disorder.  The lecture is mainly focused on the differences between normal and pathological narcissism as well as etiology, diagnosis and practical recommendations on treatment of narcissism personality disorder.

  10. Storm in My Brain: Kids and Mood Disorders (Bipolar Disorder and Depression)

    Science.gov (United States)

    ... Brain Kids and Mood Disorders (Bipolar Disorder and Depression) What is a mood disorder? Everyone feels sad, ... one part of bipolar disorder, also called manic depression. In bipolar disorder, moods change between mania (excited ...

  11. The relationship between borderline personality disorder and bipolar disorder

    Science.gov (United States)

    Zimmerman, Mark; Morgan, Theresa A.

    2013-01-01

    It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum. PMID:24174890

  12. [Comorbidity of eating disorders and bipolar affective disorders].

    Science.gov (United States)

    Kamińska, Katarzyna; Rybakowski, Filip

    2006-01-01

    Eating disorders--anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified (EDNOS) occur usually in young females. The significant pathogenic differences between patients who only restrict food, and patients with binge eating and compensatory behaviours, such as vomiting and purging were described. The prevalence of bipolar affective disorders--especially bipolar II and bipolar spectrum disorders (BS) may reach 5% in the general population. About half of the depressive episodes are associated with a "mild" bipolar disorder, and such a diagnosis is suggested by impulsivity and mood-instability. Previously, majority of research on the comorbidity between eating and affective disorders focused on depressive symptomatology, however difficulties in the reliable assessment of hypomania may obfuscate the estimation of the co-occurrence of eating disorders with BS. Epidemiological studies suggest the association between BS and eating disorders with binge episodes (bulimia nervosa, anorexia- bulimic type and EDNOS with binge episodes). Co-occurrence of such disorders with depressive symptoms probably suggests the diagnosis of BS, not recurrent depression. Bulimic behaviours, impulsivity and affective disorders might be related to the impairment of the serotonergic neurotransmission, which may result from the genetic vulnerability and early life trauma. Currently, the first-line pharmacological treatment of co-occurring eating disorders with binge episodes and BS are selective serotonin reuptake inhibitors. However in some cases, the use of mood-stabilising agents as monotherapy or in combination with serotonergic drugs may be helpful.

  13. Antisocial personality disorder and anxiety disorder: a diagnostic variant?

    Science.gov (United States)

    Coid, Jeremy; Ullrich, Simone

    2010-06-01

    Antisocial personality disorder (ASPD) with co-morbid anxiety disorder may be a variant of ASPD with different etiology and treatment requirements. We investigated diagnostic co-morbidity, ASPD criteria, and anxiety/affective symptoms of ASPD/anxiety disorder. Weighted analyses were carried out using survey data from a representative British household sample. ASPD/anxiety disorder demonstrated differing patterns of antisocial criteria, co-morbidity with clinical syndromes, psychotic symptoms, and other personality disorders compared to ASPD alone. ASPD criteria demonstrated specific associations with CIS-R scores of anxiety and affective symptoms. Findings suggest ASPD/anxiety disorder is a variant of ASPD, determined by symptoms of anxiety. Although co-morbid anxiety and affective symptoms are the same as in anxiety disorder alone, associations with psychotic symptoms require further investigation. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Meige's Syndrome: Rare Neurological Disorder Presenting as Conversion Disorder.

    Science.gov (United States)

    Debadatta, Mohapatra; Mishra, Ajay K

    2013-07-01

    Meige's syndrome is a rare neurological syndrome characterized by oromandibular dystonia and blepharospasm. Its pathophysiology is not clearly determined. A 35-year-old female presented to psychiatric department with blepharospasm and oromandibular dystonia with clinical provisional diagnosis of psychiatric disorder (Conversion Disorder). After thorough physical examination including detailed neurological exam and psychiatric evaluation no formal medical or psychiatric diagnosis could be made. The other differential diagnoses of extra pyramidal symptom, tardive dyskinesia, conversion disorder, anxiety disorder were ruled out by formal diagnostic criteria. Consequently with suspicion of Meige's syndrome she was referred to the department of Neurology and the diagnosis was confirmed. Hence, Meige's syndrome could be misdiagnosed as a psychiatric disorder such as conversion disorder or anxiety disorder because clinical features of Meige's syndrome are highly variable and affected by psychological factors and also can be inhibited voluntarily to some extent.

  15. Avoidant/Restrictive Food Intake Disorder

    Science.gov (United States)

    ... Eating Disorder Bulimia Nervosa Pica Rumination Disorder Avoidant/restrictive food intake disorder is characterized by eating very little food and/or avoiding eating certain foods. People with this disorder eat ...

  16. Anxiety disorders: Psychiatric comorbidities and psychosocial ...

    African Journals Online (AJOL)

    2018-05-24

    May 24, 2018 ... psychiatric disorders, including other anxiety disorders, mood disorders, substance use disorders ... psychiatric comorbidities present among adults at a tertiary ..... clinical files as well as unclear handwriting and missing.

  17. Panic Disorder in Children and Adolescents

    Science.gov (United States)

    ... for Families - Vietnamese Panic Disorder In Children And Adolescents No. 50; Updated July 2013 Panic disorder is a common and treatable disorder. Children and adolescents with panic disorder have unexpected and repeated periods ...

  18. Alcohol Abuse and Other Psychiatric Disorders

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS Other Psychiatric Disorders In the current Diagnostic and Statistical Manual ... and other substance use disorders are defined as psychiatric disorders. Many individuals who misuse alcohol also abuse ...

  19. Trauma, alexithymia, emotional regulation and dissociation in alcohol use disorder, substance use disorder and polysubstance disorder

    OpenAIRE

    Stark, Claire

    2017-01-01

    Background: Around 33-50% who attend treatment for substance use disorder (SUD) and alcohol use disorder (AUD) have a history of trauma. Experiencing trauma can lead to psychological disorders, difficulties with emotional regulation and dissociation. SUD and AUD can be chronic, relapsing disorders and understanding what individual factors affect addiction has important implications for treatment. Objective: The systematic review was interested in whether alexithymia affects ...

  20. [Body dysmorphic disorder].

    Science.gov (United States)

    Grau, Katharina; Fegert, Jörg Michael; Allroggen, Marc

    2015-01-01

    Body dysmorphic disorder (BDD) is a relatively common disorder with a point prevalence of 0.7-2.4 %. BDD is characterized by the patient's excessive concern with an imagined or slight defect in physical appearance. BDD usually begins in adolescence. Comorbidity rates and also suicidality rates are high. The course of BDD tends to be chronic. According to the present state of knowledge, cognitive-behavioral therapy and pharmacotherapy with selective serotonin reuptake inhibitors are valuable options in the therapy of BDD. The case report describes a recent case of BDD with typical clinical and therapy-related characteristics. The aim of this work is to strengthen the awareness of BDD in clinical practice of child and adolescent psychiatry, facilitating an adequate diagnosis and treatment of the affected individuals.