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Sample records for charcot-marie-tooth disease

  1. Charcot-Marie-Tooth Disease

    Science.gov (United States)

    Charcot-Marie-Tooth disease (CMT) is a group of genetic nerve disorders. It is named after the three doctors who first identified it. ... a nerve biopsy. There is no cure. The disease can be so mild you don't realize ...

  2. Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Reilly, Mary M

    2011-03-01

    Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder affecting at least 1 in 2,500. Over the last two decades, there have been rapid advances in understanding the molecular basis for many forms of CMT with more than 30 causative genes now described. This has made obtaining an accurate genetic diagnosis possible but at times challenging for clinicians. This review aims to provide a simple, pragmatic approach to diagnosing CMT from a clinician\\'s perspective.

  3. Genetics Home Reference: Charcot-Marie-Tooth disease

    Science.gov (United States)

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Charcot-Marie-Tooth disease Charcot- ...

  4. [Rehabilitation of Charcot-Marie-Tooth Disease].

    Science.gov (United States)

    Tajima, Fumihiro; Nakamura, Takeshi; Nishimura, Yukihide; Arakawa, Hideki; Kawasaki, Takashi; Ogawa, Takahiro; Nishiyama, Kazunari

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neuromuscular diseases causing progressive muscle weakness; contracture; deformity in the feet, legs, and hands; and impairments of ambulation and handgrip. Reduced physical ability can be attributed not only to the disease but also to physical deconditioning. Previously, most physicians in the field of rehabilitation were anxious about the hypothesis of overwork weakness in CMT, and did not conduct intensive exercise programs for patients with CMT. However, recent studies have reported that progressive resistance strengthening programs for lower extremities are feasible, safe, beneficial, and improve exercise intolerance and undue fatigue in patients with CMT. Although the improvement in exercise tolerance may be partly due to the reversal of deconditioning effect of related sedentary lifestyle, progressive resistance training and physical fitness can improve walking function, activities of daily living, and subjective perception of pain and fatigue in patients with CMT. To increase the daily physical function, some studies described the potential benefits of ankle-foot orthoses (AFOs); however, no control study supported it. So far, the training programs on CMT have been dependent on the exercise programs for able-bodied individuals. To increase the effects of rehabilitation, optimal programs that combine the training protocol and AFO strategies will have to be designed for patients with CMT. PMID:26764300

  5. Molecular Diagnosis of Charcot-Marie Tooth Disease

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The frequency of mutations in certain genes in 153 unrelated patients with Charcot-Marie-Tooth disease (CMT was determined by DNA sequencing before clinical testing at the Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, TX, and other centers.

  6. Vestibular impairment in patients with Charcot-Marie-Tooth disease

    OpenAIRE

    Poretti, A.; Palla, A; Tarnutzer, A A; Petersen, J A; Weber, K P; Straumann, D; Jung, H H

    2013-01-01

    OBJECTIVE: This case-control study aimed to determine whether the imbalance in Charcot-Marie-tooth (CMT) disease is caused only by reduced proprioceptive input or whether the involvement of the vestibular nerve is an additional factor. METHODS: Fifteen patients with CMT disease (aged 48 ± 17 years; 8 women) underwent cervical vestibular-evoked myogenic potentials, which reflect otolith-spinal reflex function, and quantitative horizontal search-coil head-impulse testing, which assesses the hi...

  7. Charcot-Marie-Tooth disease: insights from skin biopsy

    OpenAIRE

    Pisciotta, Chiara

    2015-01-01

    Inherited neuropathies, collectively known as Charcot-Marie-Tooth disease (CMT), are a group of genetically and phenotypically heterogeneous peripheral neuropathies associated with mutations or copy number variations in over 80 distinct genes. The advent of genetic testing has made sural nerve biopsy unnecessary for diagnosing most cases of CMT, particularly because the technique is somewhat invasive. Unfortunately, this has led to an inability to evaluate morphological effects by the various...

  8. Quality-of-Life in Charcot Marie Tooth Disease: The Patient's Perspective

    OpenAIRE

    Johnson, Nicholas E.; Heatwole, Chad R; Dilek, Nuran; Sowden, Janet; Kirk, Callyn A; Shereff, Denise; Shy, Michael E; Herrmann, David N.

    2014-01-01

    This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance o...

  9. Charcot-Marie-Tooth disease type 1A

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Børglum, A D; Brandt, C A; Flint, T; Bisgaard, C

    1994-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2-p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients...... with CMT type 1, using four different techniques, and identified a de novo duplication in a sporadic case. Analysis of the fully informative pVAW409R3a alleles in this family showed the duplication to be of paternal origin....

  10. Charcot-Marie-Tooth disease complicating type 2 diabetes.

    LENUS (Irish Health Repository)

    Win, Htet Htet Ne

    2012-02-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  11. Charcot-marie-tooth disease complicating type 2 diabetes.

    LENUS (Irish Health Repository)

    Win, Htet Htet Ne

    2011-07-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  12. Charcot-Marie-Tooth disease: genetic and rehabilitation aspects

    Directory of Open Access Journals (Sweden)

    Mariana CEVEI

    2008-05-01

    Full Text Available Charcot-Marie-Tooth hereditary motor and sensory neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. Typical cases have distal muscle weakness and peroneal atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and pes cavus. Hereditary neuropathies are categorized by mode of inheritance and chromosomal locus. The diagnosis is based on family history, characteristic findings on physical examination, EMG, nerve conduction velocity testing, and occasionally on nerve biopsy. The disorder shows allelic and non-allelic genetic heterogeneity, thus mutations of different genes leading to the same clinical features. Also, different mutations of the same gene may lead to different phenotypes. Molecular genetic testing is available in clinical laboratories for diagnosis of 7 subtypes of the disease. Genetic counseling and risk assessment depend on the inheritance. We present two cases with Charcot-Marie-Tooth type 1 and type 2 respectively. There is no cure for the disorder, although physical therapy and moderate activity are often recommended to maintain muscle strength and endurance.

  13. Learning about Charcot-Marie-Tooth Disease

    Science.gov (United States)

    ... and/or hearing loss, and, in some individuals, scoliosis (curvature of the spine). People with CMT disease ... MBBS, Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University Medical Center, about Charcot-Marie- ...

  14. Noncompaction Cardiomyopathy with Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available We report a case of a 53-year-old female presenting with a new-onset heart failure that was contributed secondary to noncompaction cardiomyopathy. The diagnosis was made by echocardiogram and confirmed by cardiac MRI. Noncompaction cardiomyopathy (also known as ventricular hypertrabeculation is a newly discovered disease. It is considered to be congenital (genetic cardiomyopathy. It is usually associated with genetic disorders and that could explain the genetic pathogenesis of the non-compaction cardiomyopathy. Our case had a history of Charcot-Marie-Tooth disease. There is a high incidence of arrhythmia and embolic complications. The treatment usually consists of the medical management, defibrillator placement, and lifelong anticoagulation. Heart transplantation will be the last resort.

  15. Rehabilitation issues in Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Kenis-Coskun, Ozge; Matthews, Dennis J

    2016-02-27

    Charcot Marie Tooth (CMT) disease is the most common hereditary sensorimotor neuropathy that has a slow onset. It presents usually in childhood, starting distally and from the lower limbs progressing to more proximal muscles. Due to the lack of curative medical treatments and the problematic outcomes of surgical intervention, rehabilitation continues to play a major role in treatment. This paper aims to summarize the rehabilitation approaches like aerobic, stretching and strengthening exercises. Orthotics is another important part of treatment that complete rehabilitative approaches. Orthotic devices that are currently being used and investigated in patients with CMT are also reviewed. The evidence shows that exercise is effective in improving strength and general fitness. Stretching is somewhat effective in maintaining range of motion. Orthotic devices are the mainstay of maintaining mobility and ambulation and upper extremity function. PMID:26966798

  16. Hand weakness in Charcot-Marie-Tooth disease 1X.

    LENUS (Irish Health Repository)

    Arthur-Farraj, P J

    2012-07-01

    There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.

  17. Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A

    Science.gov (United States)

    Bamford, Nigel S.; White, Klane K.; Robinett, Stephanie A.; Otto, Randolph K.; Gospe, Sidney M., Jr.

    2009-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and…

  18. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.

    LENUS (Irish Health Repository)

    Murphy, Sinead M

    2012-07-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.

  19. Auditory processing in patients with Charcot-Marie-Tooth disease type 1A.

    NARCIS (Netherlands)

    Neijenhuis, C.A.M.; Beynon, A.J.; Snik, A.F.M.; Engelen, B.G.M. van; Broek, P. van den

    2003-01-01

    HYPOTHESIS: It is unclear whether Charcot-Marie-Tooth (CMT) disease, type 1A, causes auditory processing disorders. Therefore, auditory processing abilities were investigated in five CMT1A patients with normal hearing. BACKGROUND: Previous studies have failed to separate peripheral from central audi

  20. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

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

    2016-01-01

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

  1. Disability and quality of life in Charcot-Marie-Tooth disease type 1

    OpenAIRE

    PFEIFFER, G; Wicklein, E; Ratusinski, T; Schmitt, L; Kunze, K

    2001-01-01

    OBJECTIVES—Charcot-Marie-Tooth disease type I (CMT1) is a hereditary sensorimotor neuropathy causing variable degrees of handicap. The risk for relevant disability in respect to genetic counselling is unknown. An attempt was made to define it.
METHODS—Disability and ambulation of 50 patients with CMT1 were scored by the Hauser ambulation index score and the Rankin scale. Rankin score 2 was subdivided into 2a (independent without relevant slowness) and 2b (independent, ...

  2. SMN gene analysis of the spinal form of Charcot-Marie-Tooth disease.

    OpenAIRE

    Hanash, A.; LeGuern, E.; Birouk, N; Clermont, O; Pouget, J; Bouche, P; Munnich, A; Brice, A; Melki, J

    1997-01-01

    The spinal form of Charcot-Marie-Tooth disease (spinal CMT) is a rare genetic disorder of the peripheral nervous system, the genetic basis of which remains unknown. To test the hypothesis that a defect of survival motor neuron (SMN), the determining gene for spinal muscular atrophy (SMA), would result in spinal CMT, 18 unrelated spinal CMT patients were studied. Nine of them were sporadic cases and the other nine belonged to unrelated autosomal dominant pedigrees. None of the 18 patients show...

  3. Outcome measures for Charcot-Marie-Tooth disease: clinical and neurofunctional assessment in children

    OpenAIRE

    Pagliano, Emanuela; Moroni, Isabella; Baranello, Giovanni; Magro, Anita; Marchi, Alessia; Bulgheroni, Sara; Ferrarin, Maurizio; Pareyson, Davide

    2011-01-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, presenting with symptoms often occurring since childhood, and showing a progressive course. At present, there are no valid and reliable measures for evaluation of impairment and disability in the pediatric population. The aim of this study was to determine the usefulness of outcome measures, commonly used in adult patients, in CMT children. We report the results of a comprehensive evaluation of 21 children ...

  4. Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-09-01

    The Charcot-Marie-Tooth neuropathy score (CMTNS) is a reliable and valid composite score comprising symptoms, signs, and neurophysiological tests, which has been used in natural history studies of CMT1A and CMT1X and as an outcome measure in treatment trials of CMT1A. Following an international workshop on outcome measures in Charcot-Marie-Tooth disease (CMT), the CMTNS was modified to attempt to reduce floor and ceiling effects and to standardize patient assessment, aiming to improve its sensitivity for detecting change over time and the effect of an intervention. After agreeing on the modifications made to the CMTNS (CMTNS2), three examiners evaluated 16 patients to determine inter-rater reliability; one examiner evaluated 18 patients twice within 8 weeks to determine intra-rater reliability. Three examiners evaluated 63 patients using the CMTNS and the CMTNS2 to determine how the modifications altered scoring. For inter- and intra-rater reliability, intra-class correlation coefficients (ICCs) were ≥0.96 for the CMT symptom score and the CMT examination score. There were small but significant differences in some of the individual components of the CMTNS compared with the CMTNS2, mainly in the components that had been modified the most. A longitudinal study is in progress to determine whether the CMTNS2 is more sensitive than the CMTNS for detecting change over time.

  5. Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Ohshita, Naohiro; Oka, Saeko; Tsuji, Kaname; Yoshida, Hiroaki; Morita, Shosuke; Momota, Yoshihiro; Tsutsumi, Yasuo M

    2016-01-01

    Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD. PMID:27269665

  6. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  7. Next-generation sequencing and genetic diagnosis of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2014-01-01

    Full Text Available Over 70 different Charcot-Marie-Tooth disease (CMT–associated genes have now been discovered and their number is growing. Conventional genetic testing for all CMT genes is cumbersome, expensive, and impractical in an individual patient. Next-generation sequencing (NGS technology allows cost-effective sequencing of large scale DNA, even entire exome (coding sequences or whole genome and thus, NGS platform can be employed to effectively target a large number or all CMT-related genes for accurate diagnosis. This overview discusses how NGS can be strategically used for genetic diagnosis in patients with CMT or unexplained neuropathy. A comment is made to combine simple clinical and electrophysiological algorithm to assign patients to major CMT subtypes and then employ NGS to screen for all known mutations in the subtype-specific CMT gene panel.

  8. Pé cavo adquirido na doença de Charcot-Marie-Tooth Acquired pes cavus in Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Daniel Augusto Carvalho Maranho

    2009-01-01

    Full Text Available As neuropatias sensitivomotoras hereditárias, principalmente a doença de Charcot-Marie-Tooth, manifestam-se frequentemente com o aparecimento de pé cavovaro, deformidade caracterizada pela acentuação fixa do arco plantar e inversão do retropé. O diagnóstico da doença de base e a cuidadosa avaliação do paciente fornecem os elementos-chave para decisão do tratamento. O cavo pode situar-se no antepé, retropé ou ser o resultado da associação das duas localizações. Deformidades combinadas, principalmente varismo e garras dos artelhos, devem ser bem avaliadas; as características clínicas como grau das alterações, acometimento da força muscular, flexibilidade e idade são fatores importantes para a decisão da conduta. O tratamento conservador do pé cavovaro por meio de fisioterapia, palmilhas e adaptação nos calçados é reservado ao paciente mais jovem ou casos levemente acometidos. Entretanto, há tendência de agravamento das deformidades devido à característica progressiva da doença neurológica de base. Assim, o tratamento cirúrgico pelas técnicas clássicas é indicado precocemente, sendo importante identificar as alterações primárias, diferenciá-las das secundárias e corrigi-las, se possível. As transferências musculares são usadas no sentido de minimizar o desequilíbrio, estruturas retraídas são seccionadas ou alongadas e osteotomias localizadas devem ser preferíveis às artrodeses, que são reservadas para pés rígidos e muito deformados de pacientes adultos.Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of

  9. Flexor digitorum superficialis opposition tendon transfer improves hand function in children with Charcot-Marie-Tooth disease: Case series

    OpenAIRE

    Estilow, T.; Kozin, S.H.; Glanzman, A. M.; Burns, J; Finkel, R.S.

    2012-01-01

    Charcot-Marie-Tooth disease limits hand function. Tendon transfer has not been reported in pediatric CMT. We report two severely affected children following long finger flexor digitorum superficialis opposition tendon transfer. Improvement was noted in palmar abduction, (30°/40°), opposition, (thumb to all digits), and acquisition of pincer, palmar, and lateral pinch with measureable force (1 lb). Dexterity testing improved on the 9 Hole Peg Test (1.03 s/77 s, 22 s) and Functional Dexterity T...

  10. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMTIA duplication.

    OpenAIRE

    Wise, C A; GARCIA, C. A.; Davis, S.N.; Heju, Z; Pentao, L; Patel, P.I.; Lupski, J.R.

    1993-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. One form of CMT, CMT type 1A, is characterized by uniformly decreased nerve conduction velocities, usually shows autosomal dominant inheritance, and is associated with a large submicroscopic duplication of the p11.2-p12 region of chromosome 17. A cohort of 75 unrelated patients diagnosed clinically with CMT and evaluated by electrophysiological methods were analyzed molecularly for the presence of the CMT1A ...

  11. Behavioural profiling of a murine Charcot-Marie-Tooth disease type 1A model.

    Science.gov (United States)

    Norreel, J C; Jamon, M; Riviere, G; Passage, E; Fontes, M; Clarac, F

    2001-04-01

    Different features of motor behaviour were studied on a transgenic mouse model of Charcot-Marie-Tooth's disease (CMT). Mutants with 4 or 7 copies of the human PMP22 gene leading to a phenotype significantly close to CMT's disease type 1A were compared with control animals. The aim of the study was to validate this transgenic model and to characterise the impairments occurring in the various lines. Three main types of analysis were performed in 2-month-old mice without any peculiar visible deficit: (i) a study of standardised clinical tests (SHIRPA protocol) demonstrated that only a few motor deficits were expressed; (ii) a measurement of general spontaneous activity by means of a commercial video-tracking system was performed and revealed that the main spontaneous activities were identical in the three lines with, however, some slight localised modifications; and, (iii) by contrast, the three lines respond very differently to the footprints, grip strength, splay test and rotarod test. Even in lines with a significantly limited copy number of the transgene, we observed and quantified impairments. In conclusion, mutants of CMT1A seem to be a very pertinent model of this human pathology and will certainly be useful for therapeutic procedures and for theoretical studies on this disease. PMID:11328356

  12. Vestibular impairment in Charcot-Marie-Tooth disease type 4C.

    Science.gov (United States)

    Pérez-Garrigues, Herminio; Sivera, Rafael; Vílchez, Juan Jesús; Espinós, Carmen; Palau, Francesc; Sevilla, Teresa

    2014-07-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is a hereditary neuropathy with prominent unsteadiness. The objective of the current study is to determine whether the imbalance in CMT4C is caused only by reduced proprioceptive input or if vestibular nerve involvement is an additional factor. We selected 10 CMT4C patients and 10 age-matched and sex-matched controls. We performed a comprehensive evaluation of the vestibular system, including video Head Impulse Test, bithermal caloric test, galvanic stimulation test and skull vibration-induced nystagmus test. None of the patients experienced dizziness, spontaneous or gaze-evoked nystagmus, but all had significant vestibular impairment when tested when compared to controls. Seven had completely unexcitable vestibular systems and abnormal vestibuloocular reflex. There was no correlation between the degree of vestibulopathy and age or clinical severity. Significant vestibular impairment is a consistent finding in CMT4C and is present early in disease evolution. The profound imbalance that is so disabling in these patients may result from a combination of proprioceptive loss and vestibular neuropathy, and this would modify the recommended rehabilitation strategies. PMID:24614092

  13. X inactivation in females with X-linked Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2012-07-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

  14. [Treatment for Patients with Charcot-Marie-Tooth Disease: Orthopaedic Aspects].

    Science.gov (United States)

    Watanabe, Kota

    2016-01-01

    The orthopedic manifestations in patients with Charcot-Marie-Tooth disease include deformity and dysfunction of the extremities and spine. Conservative treatment is the first choice. Orthosis and rehabilitation can improve function, and are important for the prevention of joint contractures. Foot problems are most commonly observed and require surgical treatment. Foot deformities include pes cavus, cavovarus, claw toes, or drop foot. Single or combined surgeries selected for soft tissues are plantar release, tendon transfer, or Achilles tendon lengthening, and those for bones are osteotomies and joint fusions. The upper limb initially demonstrates loss of power of the intrinsic hand muscles followed by symmetrical atrophy of the forearm muscle groups. The typical hand deformity is claw hand. Tendon transfer, joint fusion, soft tissue release, or nerve decompression procedures are performed for correction of hand deformities. Acetabular dysplasia in the hip joints is sometimes observed and osteotomy is selected as surgical treatment in such cases. The associated spinal deformity is scoliosis with or without kyphosis. Similar to treatment of idiopathic scoliosis, posterior spinal fusion is performed in patients with progressive spinal deformities. PMID:26764299

  15. Motor axon loss is associated with hand dysfunction in Charcot-Marie-Tooth disease 1a.

    NARCIS (Netherlands)

    Videler, A.J.; Dijk, J.P. van; Beelen, A.; Visser, M. de; Nollet, F.; Schaik, I.N. van

    2008-01-01

    BACKGROUND: Charcot Marie Tooth type 1a (CMT1a) is a primarily demyelinating neuropathy, characterized by slowly progressive muscle weakness, atrophy, and sensory loss, and is most pronounced in both feet and hands. There is increasing evidence that muscle weakness is determined by motor axonal dysf

  16. Doença de Charcot-Marie-Tooth: estudos eletromiográficos em 45 pacientes Charcot-Marie-Tooth disease: electromyographic studies in 45 cases

    OpenAIRE

    Marcos R. G. de freitas; Nascimento, Osvaldo J.M.; Maria T. Nevares; Tânia M. Escada

    1995-01-01

    Foi realizada eletroneuromiografia em 45 pacientes com doença de Charcot-Marie-Tooth (CMT). A classificação em tipo I e tipo II da doença de CMT foi feita com base na neurocondução motora do mediano e do ulnar. Assim 11 pacientes eram do tipo I e 34 eram do tipo II. No tipo I não houve relação entre a queda da VCN motora do ulnar e mediano com o quadro clínico da doença. Devido a ausência do potencial de ação sensitivo (PAS) do nervo sural em muitos casos, achamos impossível a classificação d...

  17. Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease

    OpenAIRE

    Huang, Jia; Wu, Xingyao; Montenegro, Gladys; Price, Justin; Wang, GaoFeng; Vance, Jeffery M.; Shy, Michael E.; Züchner, Stephan

    2009-01-01

    Hereditary peripheral neuropathies present a group of clinically and genetically heterogeneous entities. All known forms, including the various forms of Charcot-Marie-Tooth disease (CMT) are characterized as Mendelian traits and over 35 genes have been identified thus far. The mutational mechanism of the most common CMT type, CMT1A, is a 1.5 Mb chromosomal duplication at 17p12 that contains the gene PMP22. Only recently it has been realized that such copy number variants (CNV) are a widesprea...

  18. Charcot-Marie-Tooth disease and dilated cardiomyopathy. A rare combination. Enfermedad de Charcot-Marie-Tooth y miocardiopatía dilatada. Una rara asociación.

    Directory of Open Access Journals (Sweden)

    Rafael Pila Pérez

    2011-07-01

    Full Text Available

    Se presenta el caso de un paciente de 50 años de edad, con 14 años de evolución de manifestaciones clínicas, destacándose las alteraciones musculoesqueléticas de los cuatro miembros con atrofia de las prominencias tenar e hipotenar y de la musculatura de ambas piernas. Se destacó la presencia de alteraciones sensitivas en miembros inferiores con distribución en calcetín, atrofia, atonía, arreflexia y marcha equina. Desde el punto de vista cardiaco, el paciente presentaba un fibriloaleteo. La radiografía de tórax mostró un aumento marcado del área cardiaca y la ecocardiografía puso de manifiesto una miocardiopatía dilatada. El estudio histopatológico confirmó la presencia de la enfermedad de Charcot-Marie-Tooth asociada a miocardiopatía dilatada. El diagnóstico se basó en las características clínicas, la velocidad de conducción motora, y el estudio histopatológico, que demostró desmielinización con lesiones en “cebolla”, si bien faltaron los estudios genéticos. La enfermedad de Charcot-Marie-Tooth es una enfermedad rara; aproximadamente un 60 % de los pacientes que la padecen, son portadores de una duplicación del cromosoma 17. Por ello, se consideró oportuno transmitir la experiencia de este caso.

    The case of a 50 years old male patient is presented. Along 14 years of clinical evolution, four limbs musculoskeletal disorders with atrophy of the thenar and hypothenar prominences and muscles of both legs had been emphasized. The presence of sensory impairment in lower limbs with stocking distribution, atrophy, weakness, areflexia and equine gait were very peculiar in this case. From the cardiac point of view, the patient presented a fibrillation/flutter. Chest radiography showed a marked increase in the cardiac area and echocardiography revealed dilated cardiomyopathy. Histopathological examination confirmed the presence of Charcot-Marie-Tooth disease associated with dilated cardiomyopathy. While genetic

  19. Sport activity in Charcot-Marie-Tooth disease: A case study of a Paralympic swimmer.

    Science.gov (United States)

    Vita, Giuseppe; La Foresta, Stefania; Russo, Massimo; Vita, Gian Luca; Messina, Sonia; Lunetta, Christian; Mazzeo, Anna

    2016-09-01

    This study reports the positive physical, emotional and psychosocial changes induced by sport activity in a Paralympic swimmer with Charcot-Marie-Tooth (CMT) type 4A. When we compared evaluations before initiating sport activity with those after five years of competitive activity, we found: i) increased proximal muscles strength of upper limbs; ii) augmented ability to propel wheelchair independently; iii) improved quality of life; iv) reduced trait anxiety and striking improvement of depression; v) enhanced self-esteem. Longitudinal studies in large cohorts to evaluate the positive effects of sport activity are needed to support provision of evidence-based advice to patients and families. PMID:27460291

  20. Rapid genetic screening of Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies patients

    Institute of Scientific and Technical Information of China (English)

    Xiaobo Li; Kun Xia; Beisha Tang; Ruxu Zhang; Xiaohong Zi; Lin Li; Yajing Zhan; Shunxiang Huang; Jin Li; Xuning Li; Xigui Li; Zhengmao Hu

    2012-01-01

    We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.

  1. Charcot-Marie-Tooth disease and dilated cardiomyopathy. A rare combination.

    Directory of Open Access Journals (Sweden)

    Rafael Pila Pérez

    2011-07-01

    Full Text Available Se presenta el caso de un paciente de 50 años de edad, con 14 años de evolución de manifestaciones clínicas, destacándose las alteraciones musculoesqueléticas de los cuatro miembros con atrofia de las prominencias tenar e hipotenar y de la musculatura de ambas piernas. Se destacó la presencia de alteraciones sensitivas en miembros inferiores con distribución en calcetín, atrofia, atonía, arreflexia y marcha equina. Desde el punto de vista cardiaco, el paciente presentaba un fibriloaleteo. La radiografía de tórax mostró un aumento marcado del área cardiaca y la ecocardiografía puso de manifiesto una miocardiopatía dilatada. El estudio histopatológico confirmó la presencia de la enfermedad de Charcot-Marie-Tooth asociada a miocardiopatía dilatada. El diagnóstico se basó en las características clínicas, la velocidad de conducción motora, y el estudio histopatológico, que demostró desmielinización con lesiones en “cebolla”, si bien faltaron los estudios genéticos. La enfermedad de Charcot-Marie-Tooth es una enfermedad rara; aproximadamente un 60 % de los pacientes que la padecen, son portadores de una duplicación del cromosoma 17. Por ello, se consideró oportuno transmitir la experiencia de este caso.

  2. A novel mitofusin 2 gene mutation causing Charcot-Marie-Tooth type 2A disease in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    CHEING Chor Kwan; LAU Kwok Kwong; YU Kwok Wai; CHAN Yan Wo Albert; MAK Miu Chloe

    2010-01-01

    @@ Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathies, comprises a genetically heterogeneous group of inherited peripheral neuropathies. Clinically it is characterized by progressive distal weakness, muscle atrophy, distal sensory loss and loss of deep tendon reflexes. Following electrophysiological criteria, CMT is divided into two main forms: the primarily demyelinating neuropathy CMT1 with severely decreased nerve conduction velocity (NCV) (38 m/s) but decreased amplitudes.1 CMT2A, an autosomal dominant disease caused by mitofusin 2 gene (MFN2) mutations, is the most common type of CMT2, accounting for up to 33% of familial CMT2 cases.2 We reported a patient with clinical diagnosis of CMT2 caused by a novel MFN2 mutation. To our knowledge, this is a relatively early report of genetically confirmed CMT2A in Chinese.

  3. Distribución Espacial de la Enfermedad Charcot- Marie-Tooth en Costa Rica, 1990-2003 Spatial Distribution of the Charcot-Marie- Tooth Disease in Costa Rica,1990-2003

    Directory of Open Access Journals (Sweden)

    Roger E Bonilla

    2009-07-01

    Full Text Available Objetivo: Evaluar la distribución espacial como indicador de la incidencia de la enfermedad de Charcot-Marie-Tooth por los egresos hospitalarios reportados en Costa Rica entre el período 1990-2003. Métodos: Se aplicó un rastreo estadístico espacial de la incidencia de la enfermedad y se evaluó la significancia estadística de los conglomerados con excesos de casos. Resultados: El exceso de casos observados de la enfermedad en la zona de Naranjo fue estadísticamente significativo (56 versus 26.3 p Objective: To evaluate the spatial distribution of Charcot- Marie-Tooth disease as indicator of incidence in Costa Rica between 1990-2003. Methods: A spatial statistical scan was performed for the CMT incidence. We evaluated the statistical significance of high rate clusters. Results: The excess of observed cases of the disease in the area of Naranjo was statistically significant (56 vs. 26.3 p <0.05. Other regions showing significant excess of cases of CMT are: Tibás (33 vs. 13.5, Alajuela Centro (20 vs. 6, Turrialba Centro (16 vs. 4.5, Golfito (18 vs. 5.6 and Puntarenas Centro (9 vs. 1.5. Discussion: Spatial statistical scan is proposed as a tool in the decision making process in order to reduce the incidence of the disease and respond appropriately to those affected by CMT and their families. The method identifies clusters where it is necessary to focus efforts in evaluating the incidence of the disease.

  4. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.

    OpenAIRE

    Mannil, M.; Solari, A.; Leha, A.; Pelayo-Negro, A. L.; Berciano, J; Schlotter-Weigel, B.; Walter, M.C.; Rautenstrauss, B.; Schnizer, T. J.; Schenone, A.; Seeman, P; Kadian, C.; Schreiber, O.; Angarita, N. G.; Fabrizi, G.M.

    2014-01-01

    This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of ...

  5. Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies

    OpenAIRE

    Østern, Rune André Helland; Fagerheim, Toril; Hjellnes, Helene; Nygård, Bjørn; Mellgren, Svein Ivar; Nilssen, Øivind

    2013-01-01

    Background Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quali...

  6. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease

    Science.gov (United States)

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-01-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status. PMID:27162595

  7. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies. PMID:26786738

  8. PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

    2013-10-15

    Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

  9. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease.

    Science.gov (United States)

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-05-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status. PMID:27162595

  10. Genetics of Charcot-Marie-Tooth (CMT Disease within the Frame of the Human Genome Project Success

    Directory of Open Access Journals (Sweden)

    Vincent Timmerman

    2014-01-01

    Full Text Available Charcot-Marie-Tooth (CMT neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.

  11. A Novel Mutation of GDAP1 Associated with Charcot-Marie-Tooth Disease in An Iranian Family

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    Esmaeel MOHAMMADI PARGOO

    2012-06-01

    Full Text Available As a result of higher distributed consanguinity in the Mediterranean region and the Middle East, autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT are more common in these areas. CMT disease caused by mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1 gene is a severe autosomal recessive neuropathy resulting in either demyelinating CMT4A neuropathy or axonal neuropathy with vocal cord paresis. The patient was an 8-year-old boy with AR inheritance that showed some delayed achievement of motor milestones, including walking, also bilateral foot drop, wasting of distal muscles in the legs, pes cavus and marked weakness of the foot dorsiflexors. He had no hoarseness or vocal cord paralysis. Total genomic DNA was extracted from whole peripheral blood of the patient and his family by using standard procedures. PCR- sequencing method were used to analysis the whole coding regions of the GDAP1 gene. A novel homozygote insertion of T nucleotide in codon 34 was detected (c.100_101insT that probably led to an early stop codon. This mutation may be associated with a common haplotype, suggesting a common ancestor that needs further investigation in the Iranian population.

  12. Efficacy of focal mechanic vibration treatment on balance in Charcot-Marie-Tooth 1A disease: a pilot study.

    Science.gov (United States)

    Pazzaglia, Costanza; Camerota, F; Germanotta, M; Di Sipio, E; Celletti, C; Padua, L

    2016-07-01

    Patients affected by Charcot-Marie-Tooth (CMT) disease experience an impaired balance. Although the causes of the postural instability are not fully understood, somatosensory system seems to play a key role. Mechanical vibration seems to act on the somatosensory system and to improve its function. The aim of our study was to evaluate the effects of focal mechanical vibration (fMV) on the balance of CMT 1A patients. We enrolled 14 genetically confirmed CMT 1A patients (8 female and 6 male, mean age 492 years, range 32-74, mean duration of disease: 13 years, range 1-30). Patients underwent a 3-day fMV treatment on quadriceps and triceps surae and were evaluated before the treatment as well as 1 week and 1 month after the end of the treatment. The primary outcome measure was the Berg Balance Scale (BBS) and the secondary were the Dynamic Gait Index (DGI), the 6 Min Walking Test (6MWT), the muscular strength of lower limbs, the Quality of Life (QoL) questionnaire and the stabilometric variables. The statistical analysis showed a significant modification of the BBS due to the effect of treatment (p CMT 1A patients determined an improvement of balance as detected by the BBS. The concurrent improvement of stabilometric variables in the eyes closed condition only suggests that fMV acts mostly on somatosensory afferences. Further studies are needed to confirm these data on a larger sample of CMT patients. PMID:27177999

  13. Efeitos do uso de órteses na Doença de Charcot-Marie-Tooth: atualização da literatura Orthoses effects in Charcot-Marie-Tooth Disease: update

    Directory of Open Access Journals (Sweden)

    Rouse Barbosa Pereira

    2012-12-01

    Full Text Available A Doença de Charcot-Marie-Tooth (DCMT é a neuropatia periférica hereditária mais comum em seres humanos, apresentando incidência de 1:2.500 pessoas. A fraqueza distal crural na DCMT provoca inúmeras alterações na marcha, como, por exemplo, na velocidade, no comprimento, na largura e cadência dos passos. Vários recursos em reabilitação têm sido propostos para gerenciar os problemas de deambulação, dentre eles, destaca-se a utilização de órteses. O objetivo deste estudo é apresentar e discutir os resultados de estudos sobre os efeitos da utilização de órteses nos padrões de marcha na DCMT. Neste estudo foi utilizada atualização da literatura através das principais bases de dados nacionais/internacionais (SciELO, LILACS e MEDLINE, publicados entre os anos de 2006-2012. O tratamento da DCMT consiste em fisioterapia e utilização de equipamentos de assistência, visto que ainda não há fármacos ou terapia gênica capaz de atenuar os danos clínicos e funcionais. Tal associação busca maximizar a função e melhorar a qualidade de vida desses pacientes, na tentativa de evitar agravos adicionais relativos à incapacidade física. A partir de atualização de literatura é possível concluir que existe consenso sobre a utilização de órteses nos membros inferiores para promover a estabilização das articulações do tornozelo e um padrão de deambulação mais funcional, evitando sinergias inadequadas de movimento e atenuando o risco de quedas.Charcot-Marie-Tooth (CMT disease is the most common hereditary peripheral neuropathy in humans, presenting incidence of 1:2.500 people. The distal crural weakness of the CMT causes numerous gait impairment changes, for example, velocity, length, width and cadence of the steps. Several rehabilitation resources have been proposed to manage the walking problems, among them, the use of orthoses is highlighted. The objective of this study was to present and discuss the results of

  14. [An autopsy case of neuronal type Charcot-Marie-Tooth disease (HMSN type II) with nerve deafness and psychiatric symptoms].

    Science.gov (United States)

    Yoshimura, I; Yoshimura, N; Hanazono, T; Usutani, S; Muramoto, Y; Fukushima, Y

    1992-06-01

    The clinical and pathological findings of a 41-year-old male patient with atypical Charcot-Marie-Tooth disease were reported. There were 3 cases of subarachnoid haemorrhage, 2 nerve deafness and 2 hereditary motor and sensory neuropathy (HMSN) in his family. He had suffered from progressive nerve deafness since 5 years old and gait disturbance since 37 years old. He had been admitted to the psychiatric hospital 3 times because of hallucinatory-delusional state and behavior abnormalities. Neurological examinations at 39 years old revealed that he had mental deterioration (IQ 66), nerve deafness, diffuse muscle atrophy, most marked distally, sensory disturbance, areflexia, positive Romberg's sign, orthostatic hypotension, dysphagia and slurred speech. MCV of median nerve was 27.8 m/sec, and SCV was not evoked. EEG revealed nonspecific dysfunction of the brain. He died of ileus-like condition at 41 years old. General autopsy showed haemorrhagic infarction of the jejunum and ileum due to compression of the superior mesenteric artery and vein by an adhesion band of connective tissue formed after previous appendectomy. Neuropathological examinations revealed axonal degeneration and loss of myelinated fibers with schwannosis of anterior and posterior spinal nerve roots as well as peripheral nerves. The posterior roots were more severely affected than the anterior ones. Ganglion cells of the posterior root ganglia showed remarkable degeneration and loss. There was severe degeneration of the posterior columns, especially in the gracilis, of the spinal cord. Nerve cells in the anterior horns and Clarke's columns also displayed conspicuous atrophy or central chromatolysis followed by gliosis. There was slight degeneration of the posterior spinocerebellar tracts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1389565

  15. Conduction block and tonic pupils in Charcot-Marie-Tooth disease caused by a myelin protein zero p.Ile112Thr mutation.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-03-01

    We report a patient with Charcot-Marie-Tooth disease (CMT) due to the p.Ile112Thr mutation in myelin protein zero (MPZ) who presented with a patchy neuropathy with conduction block and tonic pupils. Conduction block is unusual in inherited neuropathies, while pupil abnormalities are recognised to occur in CMT especially due to MPZ mutations. This case highlights that patchy demyelinating neuropathy with conduction block may occur in p.Ile112Thr MPZ mutations. Involvement of the pupils, as in this case, may be a pointer towards a genetic rather than inflammatory cause of neuropathy.

  16. MRI findings, patterns of disease distribution, and muscle fat fraction calculation in five patients with Charcot-Marie-Tooth type 2 F disease

    Energy Technology Data Exchange (ETDEWEB)

    Gaeta, Michele; Mileto, Achille; Minutoli, Fabio; Settineri, Nicola; Donato, Rocco; Ascenti, Giorgio; Blandino, Alfredo [Policlinico ' ' G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Mazzeo, Anna; Di Leo, Rita [Policlinico ' ' G. Martino' ' , Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Messina (Italy)

    2012-05-15

    To describe the magnetic resonance imaging (MRI) pattern of muscle involvement and disease progression in five patients with late-onset Charcot-Marie-Tooth (CMT) disease type 2 F, due to a previously unknown mutation. Five patients (three males, two females) underwent MRI of the lower limbs to define the pattern of muscle involvement and evaluate the muscle fat fraction (MFF) of residual thigh muscle with gradient-echo (GRE) dual-echo dual-flip angle technique. Evaluation of fatty infiltration both by visual inspection and MFF calculation was performed. A proximal-to-distal gradient of muscle involvement was depicted in male patients with extensive muscle wasting of lower legs, less severe impairment of distal thigh muscles, and sparing of proximal thigh muscles. A peculiar phenotype finding was that no or only slight muscle abnormalities could be found in the two female patients. We described the pattern of muscle involvement and disease progression in a family with CMT disease type 2 F. GRE dual-echo dual-flip angle MRI technique is a valuable technique to obtain a rapid quantification of MFF. (orig.)

  17. A novel synonymous mutation in the MPZ gene causing an aberrant splicing pattern and Charcot-Marie-Tooth disease type 1b.

    Science.gov (United States)

    Corrado, L; Magri, S; Bagarotti, A; Carecchio, M; Piscosquito, G; Pareyson, D; Varrasi, C; Vecchio, D; Zonta, A; Cantello, R; Taroni, F; D'Alfonso, S

    2016-08-01

    Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy with a heterogeneous genetic background. Here, we describe two CMT1B families with a mild sensory-motor neuropathy and a novel synonymous variant (c.309G > T, p.G103G) in exon 3 of the MPZ gene. Next generation sequencing analysis on a 94 CMT gene panel showed no mutations in other disease genes. In vitro splicing assay and mRNA expression analysis indicated that the c.309T variant enhances a cryptic donor splice site at position c.304 resulting in the markedly increased expression of the r.304_448del alternative transcript in patients' cells. This transcript is predicted to encode a truncated P0 protein (p.V102Cfs11*) lacking the transmembrane domain, thus suggesting a possible haploinsufficiency mechanism for this mutation. This is the third reported synonymous MPZ variant associated with CMT1 and affecting splicing. These data confirm the functional impact of synonymous variants on MPZ splicing and their possible role as disease-causing mutations rather than silent polymorphisms. PMID:27344971

  18. A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-03-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 which is specific for liver and pancreas, P1a specific for liver, oocytes and embryonic stem cells, and P2 which is nerve-specific. Over 300 mutations have been described in GJB1, spread throughout the coding region. We describe two families with X-linked inheritance and a phenotype consistent with CMT1X who did not have mutations in the GJB1 coding region. The non-coding region of GJB1 was sequenced and an upstream exon-splicing variant found at approximately - 373G>A which segregated with the disease in both families and was not present in controls. This substitution is located at the last base of the nerve-specific 5\\'UTR and thus may disrupt splicing of the nerve-specific transcript. Online consensus splice-site programs predict a reduced score for the mutant sequence vs. the normal sequence. It is likely that other mutations within the GJB1 non-coding regions account for the CMT1X families who do not have coding region mutations.

  19. Examining hand dominance using dynamometric grip strength testing as evidence for overwork weakness in Charcot-Marie-Tooth disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Roberts-Clarke, Daniel; Fornusek, Che; Fiatarone Singh, Maria A; Burns, Joshua; Hackett, Daniel A

    2016-09-01

    This systematic review with a meta-analysis of studies was carried out to evaluate the potential of overwork weakness on the basis of grip strength of dominant and nondominant hands in individuals with Charcot-Marie-Tooth disease (CMT). Numerous electronic databases were searched from the earliest records to February 2016. Studies of any design including participants older than 18 years of age with a confirmed diagnosis of CMT that measured grip strength of both hands using dynamometric testing were eligible for inclusion. Of 12 593 articles identified following removal of duplicates, five articles fulfilled the criteria. A total of 166 participants, mostly with CMT1 or CMT2, were described from the studies included. Hand and finger pinch grip strength for the dominant compared with the nondominant hand was not statistically different. There is no definitive evidence that preferential use of the dominant hand in CMT impairs function relative to the nondominant hand. Thus, robust exercise trials of progressive resistance training are needed to understand the extent of adaptations possible and provide evidence of the safety of such regimens. PMID:27177353

  20. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Laurent P. Bogdanik

    2013-05-01

    Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  1. The stretcher spontaneous neurodegenerative mutation models Charcot-Marie-Tooth disease type 4D [v1; ref status: indexed, http://f1000r.es/8c

    Directory of Open Access Journals (Sweden)

    David Chandler

    2013-02-01

    Full Text Available Mice affected by a spontaneous mutation which arose within our colony exhibited a neuromuscular phenotype involving tremor and characteristic stretching of the rear limbs. The mutant, named stretcher, was used to breed a backcross cohort for genetic mapping studies. The gene responsible for the mutant phenotype was mapped to a small region on mouse chromosome 15, with a LOD score above 20. Candidate genes within the region included the Ndrg1 gene. Examination of this gene in the mutant mouse strain revealed that exons 10 to 14 had been deleted. Mutations in the human orthologue are known to result in Charcot-Marie-Tooth disease type 4D (CMT4D a severe early-onset disorder involving Schwann cell dysfunction and extensive demyelination. The stretcher mutant mouse is more severely affected than mice in which the Ndrg1 gene had been knocked out by homologous recombination. Our results demonstrate that the Ndrg1str mutation provides a new model for CMT4D, and demonstrate that exons 10 to 14 of Ndrg1 encode amino acids crucial to the appropriate function of Ndrg1 in the central nervous system.

  2. NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.

    Science.gov (United States)

    Berciano, José; Peeters, Kristien; García, Antonio; López-Alburquerque, Tomás; Gallardo, Elena; Hernández-Fabián, Arantxa; Pelayo-Negro, Ana L; De Vriendt, Els; Infante, Jon; Jordanova, Albena

    2016-02-01

    The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. By then, a working diagnosis of sporadic early onset cerebellar ataxia with peripheral neuropathy was established. Screening of mutations associated with SCA and autosomal recessive cerebellar ataxias was negative. Her son showed a mild phenotype characterized by delayed motor milestones, and lower-limb hypotonia and areflexia. Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia. PMID:26645395

  3. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. (Duke Univ. Medical Center, Durham, NC (United States)); Middleton, L.T. (Cyprus Institute of Neurology and Genetics, Nicosia (Cyprus)) (and others)

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  4. Association of the Charcot-Marie-Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance).

    Science.gov (United States)

    Boora, Ganesh K; Kulkarni, Amit A; Kanwar, Rahul; Beyerlein, Peter; Qin, Rui; Banck, Michaela S; Ruddy, Kathryn J; Pleticha, Josef; Lynch, Cynthia A; Behrens, Robert J; Züchner, Stephan; Loprinzi, Charles L; Beutler, Andreas S

    2015-10-15

    The predisposition of patients to develop polyneuropathy in response to toxic exposure may have a genetic basis. The previous study Alliance N08C1 found an association of the Charcot-Marie-Tooth disease (CMT) gene ARHGEF10 with paclitaxel chemotherapy induced peripheral neuropathy (CIPN) related to the three non-synonymous, recurrent single nucleotide variants (SNV), whereby rs9657362 had the strongest effect, and rs2294039 and rs17683288 contributed only weakly. In the present report, Alliance N08CA was chosen to attempt to replicate the above finding. N08CA was chosen because it is the methodologically most similar study (to N08C1) performed in the CIPN field to date. N08CA enrolled patients receiving the neurotoxic chemotherapy agent paclitaxel. Polyneuropathy was assessed by serial repeat administration of the previously validated patient reported outcome instrument CIPN20. A study-wide, Rasch type model was used to perform extreme phenotyping in n=138 eligible patients from which "cases" and "controls" were selected for genetic analysis of SNV performed by TaqMan PCR. A significant association of ARHGEF10 with CIPN was found under the pre-specified primary endpoint, with a significance level of p=0.024. As in the original study, the strongest association of a single SNV was seen for rs9657362 (odds ratio=3.56, p=0.018). To further compare results across the new and the previous study, a statistical "classifier" was tested, which achieved a ROC area under the curve of 0.60 for N08CA and 0.66 for N08C1, demonstrating good agreement. Retesting of the primary endpoint of N08C1 in the replication study N08CA validated the association of ARHGEF10 with CIPN. PMID:26143528

  5. Progression of motor axon dysfunction and ectopic Nav1.8 expression in a mouse model of Charcot-Marie-Tooth disease 1B.

    Science.gov (United States)

    Rosberg, Mette R; Alvarez, Susana; Klein, Dennis; Nielsen, Finn Cilius; Martini, Rudolf; Levinson, S Rock; Krarup, Christian; Moldovan, Mihai

    2016-09-01

    Mice heterozygously deficient for the myelin protein P0 gene (P0+/-) develop a slowly progressing neuropathy modeling demyelinating Charcot-Marie-Tooth disease (CMT1B). The aim of the study was to investigate the long-term progression of motor dysfunction in P0+/- mice at 3, 7, 12 and 20months. By comparison with WT littermates, P0+/- showed a decreasing motor performance with age. This was associated with a progressive reduction in amplitude and increase in latency of the plantar compound muscle action potential (CMAP) evoked by stimulation of the tibial nerve at ankle. This progressive functional impairment was in contrast to the mild demyelinating neuropathy of the tibial nerve revealed by histology. "Threshold-tracking" studies showed impaired motor axon excitability in P0+/- from 3months. With time, there was a progressive reduction in threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus associated with increasing resting I/V slope and increasing strength-duration time constant. These depolarizing features in excitability in P0+/- as well as the reduced CMAP amplitude were absent in P0+/- NaV1.8 knockouts, and could be acutely reversed by selective pharmacologic block of NaV1.8 in P0+/-. Mathematical modeling indicated an association of altered passive cable properties with a depolarizing shift in resting membrane potential and increase in the persistent Na(+) current in P0+/-. Our data suggest that ectopic NaV1.8 expression precipitates depolarizing conduction failure in CMT1B, and that motor axon dysfunction in demyelinating neuropathy is pharmacologically reversible. PMID:27215377

  6. Mutation Analysis of Gap Junction Protein Beta 1 and Genotype-Phenotype Correlation in X-linked Charcot-Marie-Tooth Disease in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Bo Sun; Zhao-Hui Chen; Li Ling; Yi-Fan Li; Li-Zhi Liu; Fei Yang; Xu-Sheng Huang

    2016-01-01

    Background:Among patients with Charcot-Marie-Tooth disease (CMT),the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type,accounting for approximately 90% of all CMTX.More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32).CX32 is thought to form gap junctions that promote the diffusion pathway between cells.GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin,and novel mutations are continually discovered.Methods:We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People's Liberation Army General Hospital from December 20,2012,to December 31,2015.Clinical examination,nerve conduction studies,and molecular and bioinformatics analyses were performed to identify patients with CMTX 1.Results:Nine GJB1 mutations (c.283G>A,c.77C>T,c.643C>T,c.515C>T,c.191G>A,c.610C>T,c.490C>T,c.491G>A,and c.44G>A) were discovered in nine patients.Median motor nerve conduction velocities of all nine patients were < 38 m/s,resembling CMT Type 1.Three novel mutations,c.643C>T,c.191G>A,and c.610C>T,were revealed and bioinformatics analyses indicated high pathogenicity.Conclusions:The three novel missense mutations within the GJB1 gene broaden the mutational diversity of CMT 1 X.Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.

  7. Systemic inflammation disrupts oligodendrocyte gap junctions and induces ER stress in a model of CNS manifestations of X-linked Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Olympiou, Margarita; Sargiannidou, Irene; Markoullis, Kyriaki; Karaiskos, Christos; Kagiava, Alexia; Kyriakoudi, Styliana; Abrams, Charles K; Kleopa, Kleopas A

    2016-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is a common form of inherited neuropathy resulting from different mutations affecting the gap junction (GJ) protein connexin32 (Cx32). A subset of CMT1X patients may additionally present with acute fulminant CNS dysfunction, typically triggered by conditions of systemic inflammation and metabolic stress. To clarify the underlying mechanisms of CNS phenotypes in CMT1X we studied a mouse model of systemic inflammation induced by lipopolysaccharide (LPS) injection to compare wild type (WT), connexin32 (Cx32) knockout (KO), and KO T55I mice expressing the T55I Cx32 mutation associated with CNS phenotypes. Following a single intraperitoneal LPS or saline (controls) injection at the age of 40-60 days systemic inflammatory response was documented by elevated TNF-α and IL-6 levels in peripheral blood and mice were evaluated 1 week after injection. Behavioral analysis showed graded impairment of motor performance in LPS treated mice, worse in KO T55I than in Cx32 KO and in Cx32 KO worse than WT. Iba1 immunostaining revealed widespread inflammation in LPS treated mice with diffusely activated microglia throughout the CNS. Immunostaining for the remaining major oligodendrocyte connexin Cx47 and for its astrocytic partner Cx43 revealed widely reduced expression of Cx43 and loss of Cx47 GJs in oligodendrocytes. Real-time PCR and immunoblot analysis indicated primarily a down regulation of Cx43 expression with secondary loss of Cx47 membrane localization. Inflammatory changes and connexin alterations were most severe in the KO T55I group. To examine why the presence of the T55I mutant exacerbates pathology even more than in Cx32 KO mice, we analyzed the expression of ER-stress markers BiP, Fas and CHOP by immunostaining, immunoblot and Real-time PCR. All markers were increased in LPS treated KO T55I mice more than in other genotypes. In conclusion, LPS induced neuroinflammation causes disruption of the main astrocyte

  8. Clinical classification and gene mutation of Chinese probands with Charcot-Marie-Tooth disease Analysis of 57 cases

    Institute of Scientific and Technical Information of China (English)

    Ruxu Zhang; Xiaobo Li; Xiaohong Zi; Shunxiang Huang; Fufeng Zhang; Kun Xia; Qian Pan; Beisha Tang

    2011-01-01

    Charcot-Mafie-Tooth (CMT) disease is the most common inherited peripheral neuropathic disorder.CMT is clinically and genetically heterogeneous. To date, 27 genes associated with the disease have been cloned. The present study carried out clinical classification according to clinical,electrophysiological and pathological features, conducted inheritance classification according to inheritance patterns, and performed mutation analysis of 13 CMT disease genes (PMP22, CX32,HSPB1, MNF2, MPZ, HSPB8, GDAP1, NFL, EGR2, SIMPLE, RAB7, LMNA, MTMR2) in 57 Chinese probands with CMT. Five cases of AD-CMT1 and 13 cases of sporadic CMT1 were diagnosed as CMT1A; five cases of X-CMT1, one case of X-CMT2 and one case of sporadic CMT1 were diagnosed as CMTX1; four cases of AD-CMT2 were diagnosed as CMT2F; one case of AD-CMT2 and one case of sporadic CMT2 were diagnosed as CMT2A2; one case of AD-CMT2 was diagnosed as CMT2L; one case of AD-CMT2 was diagnosed as CMT2J; one case of AR-CMT1 was diagnosed as CMT4A. Among the 57 CMT probands, seven genotypes were determined among 34 patients, with a detection rate of 59.6%. The results indicated that the clinical classification and inheritance classification are indispensable for selecting potential disease genes for mutation detection, and for efficient molecular diagnosis.

  9. Charcot-Marie-Tooth Disease

    Science.gov (United States)

    ... CMT1 typically show signs of abnormal myelination. Specifically, "onion bulb" formations may be seen which represent axons ... research involves gene therapy experiments. Research with cell cultures and animal models has shown that it is ...

  10. Hip Subluxation, first clinical manifestation in a boy with illness of Charcot Marie Tooth

    International Nuclear Information System (INIS)

    Charcot-Marie-Tooth disease is a motor and sensitive neuropathy characterized by limb atrophy and weakness, cavus feet and in some cases acetabular dysplasia. We present a case of bilateral hip subluxation caused by this disease, which needed surgical correction

  11. Hereditaer motorisk sensorisk neuropati (Charcot-Marie-Tooths sygdom). Molekyloergenetiske aspekter

    DEFF Research Database (Denmark)

    Hertz, M J; Børglum, Anders; Brandt, C A; Bisgård, C

    1995-01-01

    Hereditary motor and sensory neuropathy (HMSN) comprises a heterogenous group of peripheral neuropathies which are classified on the basis of symptoms, mode of inheritance and electrophysiological and neuropathological investigations. HMSN type I, or Charcot-Marie-Tooth disease (CMT) type 1, is a...

  12. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients.

    Science.gov (United States)

    Mannil, Manoj; Solari, Alessandra; Leha, Andreas; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Walter, Maggie C; Rautenstrauss, Bernd; Schnizer, Tuuli J; Schenone, Angelo; Seeman, Pavel; Kadian, Chandini; Schreiber, Olivia; Angarita, Natalia G; Fabrizi, Gian Maria; Gemignani, Franco; Padua, Luca; Santoro, Lucio; Quattrone, Aldo; Vita, Giuseppe; Calabrese, Daniela; Young, Peter; Laurà, Matilde; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Shy, Michael E; Reilly, Mary M; Pareyson, Davide; Sereda, Michael W

    2014-11-01

    This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures - the 10m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry - further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials. PMID:25085517

  13. A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K

    Directory of Open Access Journals (Sweden)

    Cassereau Julien

    2011-12-01

    Full Text Available Abstract Background The ganglioside-induced differentiation-associated protein 1 gene (GDAP1, which is involved in the Charcot-Marie-Tooth disease (CMT, the most commonly inherited peripheral neuropathy, encodes a protein anchored to the mitochondrial outer membrane. The phenotypic presentations of patients carrying GDAP1 mutations are heterogeneous, making it difficult to determine genotype-phenotype correlations, since the majority of the mutations have been found in only a few unrelated patients. Locus-specific databases (LSDB established in the framework of the Human Variome Project provide powerful tools for the investigation of such rare diseases. Methods and Results We report the development of a publicly accessible LSDB for the GDAP1 gene. The GDAP1 LSDB has adopted the Leiden Open-source Variation Database (LOVD software platform. This database, which now contains 57 unique variants reported in 179 cases of CMT, offers a detailed description of the molecular, clinical and electrophysiological data of the patients. The usefulness of the GDAP1 database is illustrated by the finding that GDAP1 mutations lead to primary axonal damage in CMT, with secondary demyelination in the more severe cases of the disease. Conclusion Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases.

  14. Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-α6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C.

    Science.gov (United States)

    Vijay, Sauparnika; Chiu, Meagan; Dacks, Joel B; Roberts, Rhys C

    2016-07-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is one of the commonest autosomal recessive inherited peripheral neuropathies and is associated with mutations in the Rab11 effector, SH3TC2. Disruption of the SH3TC2-Rab11 interaction is the molecular abnormality underlying this disease. However, why SH3TC2 mutations cause an isolated demyelinating neuropathy remains unanswered. Here we show that SH3TC2 is an exclusive Schwann cell protein expressed late in myelination and is downregulated following denervation suggesting a functional role in myelin sheath maintenance. We support our data with an evolutionary cell biological analysis showing that the SH3TC2 gene, and its paralogue SH3TC1, are derived from an ancestral homologue, the duplication of which occurred in the common ancestor of jawed vertebrates, coincident with the appearance of Schwann cells and peripheral axon myelination. Furthermore, we report that SH3TC2 associates with integrin-α6, suggesting that aberrant Rab11-dependent endocytic trafficking of this critical laminin receptor in myelinated Schwann cells is connected to the demyelination seen in affected nerves. Our study therefore highlights the inherent evolutionary link between SH3TC2 and peripheral nerve myelination, pointing also towards a molecular mechanism underlying the specific demyelinating neuropathy that characterizes CMT4C. PMID:27068304

  15. An Algorithm for Genetic Testing of Serbian Patients with Demyelinating Charcot-Marie-Tooth

    OpenAIRE

    Keckarevic Markovic, Milica P.; Dackovic, Jelena; Mladenovic, Jelena; Milic-Rasic, Vedrana; Kecmanovic, Miljana; Keckarevic, Dusan; Romac, Stanka

    2013-01-01

    Charcot-Marie Tooth (CMT) is a clinically and genetically heterogeneous group of diseases with rough genotype–phenotype correlation, so the final diagnosis requires extensive clinical and electrophysiological examination, family data, and gene mutation analysis. Although there is a common pattern of genetic basis of CMT, there could be some population differences that should be taken into account to facilitate analyses. Here we present the algorithm for genetic testing in Serbian patients wit...

  16. Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A

    NARCIS (Netherlands)

    J.P. van Dijk; C. Verhamme; I.N. van Schaik; H.J. Schelhaas; E. Mans; L.J. Bour; D.F. Stegeman; M.J. Zwarts

    2010-01-01

    Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with comp

  17. Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A.

    NARCIS (Netherlands)

    Dijk, J.P. van; Verhamme, C.; Schaik, I.N. van; Schelhaas, H.J.; Mans, E.; Bour, L.J.; Stegeman, D.F.; Zwarts, M.J.

    2010-01-01

    BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with comp

  18. Heterogeneity in the properties of NEFL mutants causing Charcot-Marie-Tooth disease results in differential effects on neurofilament assembly and susceptibility to intervention by the chaperone-inducer, celastrol.

    Science.gov (United States)

    Gentil, Benoit J; Mushynski, Walter E; Durham, Heather D

    2013-07-01

    Aberrant aggregation of neurofilament proteins is a common feature of neurodegenerative diseases. For example, neurofilament light protein (NEFL) mutants causing Charcot-Marie-Tooth disease induce misassembly of neurofilaments. This study demonstrated that mutations in different functional domains of NEFL have different effects on filament assembly and susceptibility to interventions to restore function. The mouse NEFL mutants, NEFL(Q333P) and NEFL(P8R), exhibited different assembly properties in SW13-cells, cells lacking endogenous intermediate filaments, indicating different consequences of these mutations on the biochemical properties of NEFL. The p.Q333P mutation caused reversible misfolding of the protein. NEFL(Q333P) could be refolded and form coil-coiled dimers, in vitro using chaotropic agent, and in cultured cells by induction of HSPA1 and HSPB1. Celastrol, an inducer of chaperone proteins, induced HSPA1 expression in motor neurons and prevented the formation of neurofilament inclusions and mitochondrial shortening induced by expression of NEFL(Q333P), but not in sensory neurons. Conversely, celastrol had a protective effect against the toxicity of NEFL(P8R), a mutant which is sensitive to HSBP1 but not HSPA1 chaperoning, only in large-sized sensory neurons, not in motor neurons. Importantly, sensory and motor neurons do not respond identically to celastrol and different chaperones are upregulated by the same treatment. Thus, effective therapy of CMT not only depends on the identity of the mutated gene, but the consequences of the specific mutation on the properties of the protein and the neuronal population targeted. PMID:23618875

  19. Irradiação contralateral de força para a ativação do músculo tibial anterior em portadores da doença de Charcot-Marie-Tooth: efeitos de um programa de intervenção por FNP Contralateral force irradiation for the activation of tibialis anterior muscle in carriers of Charcot-Marie-Tooth disease: effect of PNF intervention program

    Directory of Open Access Journals (Sweden)

    Paula C. Meningroni

    2009-10-01

    Full Text Available OBJETIVO: Avaliar a resposta do músculo tibial anterior (TA após um protocolo de cinco semanas com irradiação contralateral de força através de diagonais de facilitação neuromuscular proprioceptiva (FNP em pacientes com polineuropatia desmielinizante associada à doença de Charcot-Marie-Tooth do tipo 1A (CMT-1A. MÉTODOS: Participaram deste estudo 12 pacientes, de ambos os sexos. Eles foram tratados em uma frequência de duas vezes por semana, durante cinco semanas. Em cada sessão, foram utilizadas as diagonais de Chopping, extensão-adução com rotação interna (EARI e flexão-abdução com rotação interna (FARI. As diagonais foram repetidas quatro vezes, em ambos os membros superiores e inferiores; cada diagonal tinha duração média de 6 segundos. Durante as execuções, a resposta muscular do TA foi registrada por um eletromiógrafo de superfície, desprezando-se os 2 segundos iniciais e finais de cada diagonal. A média dos valores de Root Mean Square (RMS das quatro repetições foi normalizada em porcentagem. Os dados iniciais e finais foram submetidos ao teste em t para amostras pareadas com valores de p significativos OBJECTIVE: To evaluate the response of the tibialis anterior (TA muscle following a five-week protocol with contralateral irradiation force through Proprioceptive Neuromuscular Facilitation (PNF diagonals in patients with demyelinating polyneuropathy associated with Charcot-Marie-Tooth disease type 1A (CMT-1A. METHODS: The study included 12 patients of both sexes. They were treated twice-weekly for 5 weeks. At each session, they performed the following diagonal patterns: chopping, extension-adduction with internal rotation (EAIR and flexion-abduction with internal rotation (FAIR. The diagonals were repeated four times, in both upper and lower limbs, with each repetition lasting six seconds on average. During execution, the response of the TA muscle was recorded by a surface electromyograph disregarding the

  20. Electrophysiological Evaluation of Chronic Inflammatory Demyelinating Polyneuropathy and Charcot-Marie-Tooth Type 1: Dispersion and Correlation Analysis

    OpenAIRE

    Kang, Ji Hyuk; Kim, Hye Jeong; Lee, Eun Ryeong

    2013-01-01

    [Purpose] The purpose of this study was to analyze and compare electrophysiological characteristics observed in nerve conduction studies (NCS) of chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot-Marie-Tooth disease type 1 (CMT 1). [Subjects] A differential diagnosis of acquired and congenital demyelinating neuropathies was based on a study of 35 patients with NCS-confirmed CIDP and 30 patients with CMT 1 genetically proven by peripheral myelin protein-22 (PMP-22) gene anal...

  1. Charcot-Marie-Tooth and Related Diseases

    Science.gov (United States)

    ... does, and it isn’t contagious. It’s hereditary, meaning that it can be passed down through a ... easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types of CMT ...

  2. Denaturing high-performance liquid chromatography of the myotubularin-related 2 gene (MTMR2) in unrelated patients with Charcot-Marie-Tooth disease suggests a low frequency of mutation in inherited neuropathy.

    Science.gov (United States)

    Bolino, A; Lonie, L J; Zimmer, M; Boerkoel, C F; Takashima, H; Monaco, A P; Lupski, J R

    2001-03-01

    Charcot-Marie-Tooth type 4B (CMT4B), an autosomal recessive demyelinating neuropathy characterized by focally folded myelin sheaths in the peripheral nerve, has been associated with mutations in the gene encoding myotubularin-related protein 2, MTMR2, on chromosome 11q22. To investigate whether mutations in MTMR2 may also cause different forms of CMT, we screened 183 unrelated patients with a broad spectrum of CMT and related neuropathies using denaturing high-performance liquid chromatography. We identified four frequent and three rare exonic variants; two of the rare variants were identified in two unrelated patients with congenital hypomyelinating neuropathy and not in the normal controls. Our results suggest that loss-of-function mutations in MTMR2 are preferentially associated with the CMT4B phenotype. PMID:11354824

  3. Neurophysiological performance of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type 1)%脱髓鞘型腓骨肌萎缩症的神经电生理表现

    Institute of Scientific and Technical Information of China (English)

    王娆; 诸寅; 杨卓; 王丽华; 杨昀; 张珍珍

    2013-01-01

    Objective To find out the neurophysiological performance of Charcot-Marie-Tooth disease (CMT) of hereditary motor and sensory neuropathy (HMSN) type 1,and provide examination basis for clinical diagnosis and Ureatment of the disease.Methods Sixty-two patients with CMT of HMSN type 1,admitted to our hospital from January 2011 to December 2012 were chosen in our study; the nerve conduction velocity,including motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV),and electromyogram (EMG) of these patients were examined.All the test results were analyzed statistically.Results MNCV in different nerves could not be detected in 35 patients,counting for 56.5%; removing the cases that MNCV not being elicited,average test results of tibial nerve,common peroneal nerve and median nerve MNCV were (23.48±9.60) m/s,(26.35±9.14) m/s and (30.07±12.19) m/s.SNCV in different nerves could not be detected in 50 patients,counting for 80.6%; removing the cases that SNCV not being elicited,average test results of common peroneal nerve and median nerve MNCV were (28.06±10.32) m/s and (31.20±12.05) m/s.Totally,175 muscles were inspected by EMG; among them,109 neurogenic muscles were determined,counting for 62.3%; 14 muscles were diagnosed as having suspect neurogenic damage,counting for 8.0%; 52 normal muscles were noted,counting for 29.7 %.There were 53 of neurogenic damages in 62 cases,counting for 85.5%; among them,the distal neurogenic muscles damages were in 47 cases; while proximal neurogenic muscle damages were in 11 cases.Conclusion The neurophysiological manifestations of CMT patients of HMSN type 1 are different and changes following the patient's age,duration and examination site.%目的 分析脱髓鞘型(HMSN 1型)腓骨肌萎缩症的神经电生理表现,为该疾病的临床诊断治疗提供检查依据.方法 选取自2011年1月至2012年12月北京积水潭医院收治的62例HMSN 1型腓骨肌萎缩症患者,行神经传导

  4. Thr(118Met amino acid substitution in the peripheral myelin protein 22 does not influence the clinical phenotype of Charcot-Marie-Tooth disease type 1A due to the 17p11.2-p12 duplication

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    W. Marques Jr.

    2003-10-01

    Full Text Available The Thr(118Met substitution in the peripheral myelin protein 22 (PMP22 gene has been detected in a number of families with demyelinating Charcot-Marie-Tooth (CMT1 neuropathy or with the hereditary neuropathy with liability to pressure palsy, but in none of them has it consistently segregated with the peripheral neuropathy. We describe here a CMT1 family (a 63-year-old man, his brother and his niece in which two mutations on different chromosomes were found in the PMP22 gene, the 17p duplication, detected by fluorescent semiquantitative polymerase chain reaction (PCR of microsatellite markers localized within the duplicated region on chromosome 17p11.2-p12, and the Thr(118Met substitution, detected by direct sequencing the four coding exons of the PMP22 gene. A genotype/phenotype correlation study showed that the neuropathy segregates with the duplication and that the amino acid substitution does not seem to modify the clinical characteristics or the severity of the peripheral neuropathy. We did not find any evidence to characterize this substitution as a polymorphism in the population studied and we propose that the high frequency reported for this point mutation in the literature suggests that the Thr(118Met substitution may be a hotspot for mutations in the PMP22 gene.

  5. Rehabilitation Management of the Charcot-Marie-Tooth Syndrome: A Systematic Review of the Literature.

    Science.gov (United States)

    Corrado, Bruno; Ciardi, Gianluca; Bargigli, Chiara

    2016-04-01

    The Charcot-Marie-Tooth disease (CMT) causes significant muscular deficits in the affected patients, restricts daily activities (ADL), and involves a severe disability. Although the conservative intervention is the only treatment for the disease, there is no scientific evidence so far on rehabilitation treatment. Objectives of the review are: research the best literary evidence so far on the rehabilitation treatment of CMT; critically analyze the outcome, to build an evidence-based work protocol.A systematic review of the rehabilitation of a patient with CMT, including the results from the following databases: Pubmed, Medline, Embase, Pedro, Cinahl, Ebsco discovery. Criteria for inclusion: randomized/controlled studies, analytic studies, transversal studies on a cohort of at least 10 individuals; medium/long-term report of the results.Eleven studies in total have been admitted to the final review phase; trials about physiotherapy CMT treatment (5), about orthosis treatment (6). Despite the wide range of outcomes and proposed interventions, the data points to the following: strength or endurance trainings improve functionality and ADLs of affected patients, while orthotic role is, at the moment, not completely clear.Physiotherapy treatment is a useful tool to manage CMT; more studies on a larger number of cases are needed to define orthosis utility and to establish the gold standard of the treatment. PMID:27124017

  6. [Phenotypes of Charcot-Marie-Tooth Syndrome and Differential Diagnosis Focused in Inflammatory Neuropathies].

    Science.gov (United States)

    Iijima, Masahiro

    2016-01-01

    Charcot-Marie-Tooth disease (CMT), the most frequent form of inherited neuropathy, is a genetically heterogeneous syndrome of the peripheral nervous system with a rather homologous clinical phenotype (slowly progressive distal weakness and muscle atrophy, skeletal deformities, and areflexia in each limb). CMT1 is the autosomal-dominant demyelinating form, and CMT1A (mostly PMP22 duplication) is the most frequent subtype, followed by CMTX1, HNPP (hereditary neuropathy with liability to pressure palsies), CMT1B, or CMT2. As CMT is characterized by slowly progressive motor and sensory disturbances in each limb, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) occasionally. Some points can distinguish demyelinating CMT from CIDP. CMT1 patients do not show the conduction block that is frequent in CIDP. In addition, ultrasonographic findings are useful because CMT1 suggests diffuse enlargement of peripheral nerves, whereas CIDP is characterized by asymmetrical or focal enlargement of peripheral nerves. Some CMT1 cases show favorable responses to immunomodulating therapeutics such as corticosteroids, IVIg, and plasma exchange. Such CIDP-like CMT1 (especially CMT1B or CMT2A) shows moderate to high levels of cerebrospinal fluid protein and infiltrated inflammatory macrophages. PMID:26764297

  7. Oral Health, Temporomandibular Disorder, and Masticatory Performance in Patients with Charcot-Marie-Tooth Type 2

    Directory of Open Access Journals (Sweden)

    Rejane L. S. Rezende

    2013-01-01

    Full Text Available Background. The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2. Methods and Results. The average number of decayed, missing, and filled teeth (DMFT for both groups, control (CG and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P=0.227. The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P=0.899. The prevalence of self-reported TMD was 33.3% and 38.9% (P=0.718 in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG and 22.2% (CMT2, without significant difference between groups (P=0.162. The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7% and temporalis (CG = 19.0%; GCMT2 = 33.3% muscle pain. The geometric mean diameter (GMD was not significantly different between groups (CG = 4369; CMT2 = 4627, P=0.157. Conclusion. We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance.

  8. A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis%伴声带麻痹的X连锁腓骨肌萎缩症GJB1基因新突变

    Institute of Scientific and Technical Information of China (English)

    李清华; 蒋静子; 刘开祥; 俸军林; 曾爱源; 李浩; 吴岚; 唐永刚; 陈梅玲; 林小慧

    2010-01-01

    Objective To report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1). Methods Part of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals. Results Eight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c. 186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype. Conclusion Respiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.%目的 报告1个临床可疑的伴声带麻痹的X连锁显性遗传腓骨肌萎缩症(X-1inked Charcot-Marie-Tooth disease,CMTX)家系,并探讨与连接蛋白(gap jurction protein beta 1,GJB1)基因突变的关系.方法 对1个具有声音嘶哑、吞咽困难、致死性呼吸衰竭的临床可疑的CMTX家系进行临床、纤维喉镜、头部MRI及电生理检

  9. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

    Directory of Open Access Journals (Sweden)

    A-ping Sun

    2015-01-01

    Full Text Available Charcot-Marie-Tooth disease type 1A (CMT1A is caused by duplication of the peripheral myelin protein 22 (PMP22 gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.

  10. Causes of Charcot-Marie-Tooth Disease (CMT)

    Science.gov (United States)

    ... does, and it isn’t contagious. It’s hereditary, meaning that it can be passed down through a ... easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types of CMT ...

  11. Clinical and electrophysiological characteristics of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation%周围髓鞘蛋白22基因重复突变致夏科-马里-图斯病1A亚型的临床和神经电生理特征

    Institute of Scientific and Technical Information of China (English)

    汪仁斌; 严莉; 段晓慧; 毛坤; 孙少杰; 董明睿; 焦劲松; 王国相

    2012-01-01

    目的 探讨周围髓鞘蛋白22(PMP22)基因重复突变阳性的夏科-马里-图斯病(CMT) 1A亚型患者临床和神经电生理改变特点.方法 总结21例PMP22基因重复突变阳性的CMT1A患者的临床特点,并分析其神经电生理特征.结果 21例患者中,10例临床特征符合四肢远端萎缩无力的典型CMT1型表现,另外11例呈不典型性,如仅有头晕、合并听力障碍、上肢姿势性震颤、反复发作性肢体无力、伴有小脑性共济失调及癫(痢)等.10例患者肌电图出现纤颤电位和(或)正锐波,15例患者运动单位电位时限延长.神经传导存在广泛异常,所有患者被检的运动或感觉神经传导速度存在不同程度的减慢或消失.结论 PMP22重复突变阳性的CMT1A患者具有较高的临床异质性,其电生理特点为肌电图呈神经源性损害,感觉神经病变重于运动神经,下肢受累程度重于上肢,神经电生理检查对CMT1A的诊断很重要.%Objective To investigate the clinical and electrophysiological characteristics in Charcot-Marie-Tooth disease(CMT ) type 1A patients with (peripheral myetin protein22,PMP22) duplication mutation. Methods Twenty one patients with CMT 1A were retrospectively studied. Routine electromyography ( EMG) and nerve conduction had been performed in all patients. Hie clinical and electrophysiological features were analyzed. Results 10 of 21 patients showed typical presentations including weakness and atrophy in the distal parts of limbs, and 11 atypical cases with special phenotypes including mild dizziness, hearing loss, postural tremor in the upper limbs, recurrent limbs weakness , cerebellar ataxia and epilepsy. EMG detected fibrillation potentials and positive sharp waves in 10 patients and prolonged duration of motor unit potentials in 15 patients respectively. Nerve conduction studies revealed decreased nerve conductive velocity or unelicited potentials in all detected nerves in the patients. Conclusion The CMT 1

  12. 腓骨肌萎缩症(CMT)1型的临床、神经电生理及CMT1A型基因诊断方法的研究%Study on the clinic, neuro-electrophysiology of Charcot-Marie-Tooth disease type 1 and the gene diagnosis methods of CMT1 A

    Institute of Scientific and Technical Information of China (English)

    史磊; 曹秉振

    2013-01-01

    目的 观察腓骨肌萎缩症(CMT)1型患者的临床表现及神经电生理特点,同时利用两种不同方法检测CMT1A型相关基因是否存在突变,并分析两种方法的临床应用价值以进一步确定CMT1A型的诊断.方法 对临床确诊为CMT1型的5例患者进行详细的临床及神经电生理检查,同时对所有患者利用等位基因特异性PCR及MLPA两种方法进行PMP22基因重复突变检测.结果 4例患者20岁前发病,其中2例有家族史,1例患者30岁左右发病.临床特点为进行性四肢远端无力伴肌萎缩,四肢远端感觉减退,腱反射均减弱或消失,2例患者出现弓型足.神经电生理检查示神经传导速度减慢,波幅轻度降低.两种基因检测均发现1例患者存在PMP22基因重复突变.结论 CMT1型发病年龄较早,主要表现为进行性四肢无力伴肌萎缩,神经电生理可见神经传导速度明显降低,波幅略有降低.等位基因特异性PCR和MLPA两种方法检测基因突变结果一致.%Objective To study the clinical and neuro-electrophysiological features of Charcot-Marie-Tooth type 1. Two methods were combined to detect mutations in CMT 1A - related genes and comparison of the two methods was performed to determine the clinical value for further diagnosis of CMT1 A. Methods 5 cases of patients with CMT1 underwent detailed clinical and neuro-electrophysiology examinations. Allele-specific PCR and multiplex ligation-dependent probe amplification type CMT1 ( MLPA-CMT1) were respectively used to detect PMP22 gene duplication mutation in 5 cases. Results Two cases has a family history. age at onset was in the first or second decade except one patient. The clinical features were slowly progressive distalmuscle weakness , atrophy and end - brush form sensory decrement, diminshed or absent tendon reflexes. There are foot deformity in 2 patients. EMG showed conduction velocities highly decreased and volatility decreased slightly. One patient was detected

  13. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker.

    Science.gov (United States)

    Nobbio, Lucilla; Visigalli, Davide; Radice, Davide; Fiorina, Elisabetta; Solari, Alessandra; Lauria, Giuseppe; Reilly, Mary M; Santoro, Lucio; Schenone, Angelo; Pareyson, Davide

    2014-06-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A. PMID:24812204

  14. Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

    Directory of Open Access Journals (Sweden)

    Mélodie Aubart

    Full Text Available BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects. Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2 disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II

  15. Diagnóstico clínico de la enfermedad Charcot-Marie-Tooth

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    Yuselis Pérez Cid

    2014-08-01

    Full Text Available La enfermedad de Charcot-Marie-Tooth es un trastorno polineuropático genéticamente heterogéneo, en la que se han identificado más de 30 genes responsables; sin embargo, el diagnóstico es posible establecerlo sobre las bases de los estudios clínicos y electrofisiológicos. Constituye un reto en la práctica médica de los países del tercer mundo contar con la realización sistemática de estudios genéticos moleculares de las neuropatías hereditarias, por lo que en este trabajo se enfatiza en los estudios clínico-electrofisiológicos para la clasificación de la CMT

  16. Assessment of upper motor neuron dysfunction by triple stimulation technique in patients with Charcot-Marie-Tooth disease%三重刺激技术对腓骨肌萎缩症上运动神经元损害的评估

    Institute of Scientific and Technical Information of China (English)

    徐迎胜; 张朔; 刘小璇; 孙阿萍; 樊东升

    2016-01-01

    目的 对腓骨肌萎缩症(CMT)患者进行三重刺激技术(TST)检测,探索其上运动神经元(UMN)损害的亚临床证据,以期为致病基因的筛选提供依据.方法 分析2013年8月至2015年8月于北京大学第三医院神经内科就诊的经基因检测确诊的CMT患者65例.对其进行临床查体、神经电生理检测,主要观察锥体束征和TST检测(包括经颅磁刺激、外周神经刺激、对冲技术等)结果,计算TST test/TST control波幅比,判断其上运动神经元功能状况.结果 临床查体发现7例患者下肢腱反射亢进,Babinski征阳性,肌张力增高,其中2例合并上肢腱反射亢进,Hoffmann征阳性.10例患者TST test/TST control波幅比下降(其中5例下肢腱反射亢进,Babinski征阳性,2例合并上肢腱反射亢进,Hoffmann征阳性).对应的致病基因:MFN2基因突变5例,BSCL2基因突变1例,3例GJB1基因突变,GDAP基因突变1例.根据临床查体和TST结果,18.5%(12例)的患者存在上运动神经元损害.结论 CMT患者可存在上运动神经元损害,据此可进行相关致病基因检测.%Objective To investigate the presence of upper motor neuron dysfunction in patients with Charcot-Marie-Tooth disease (CMT) by triple stimulation technique (TST) to provide evidence for gene diagnosis.Methods A total of 65 CMT patients confirmed by genetic testing from Peking University Third Hospital between August 2013 and August 2015,underwent physical examination and routine electrophysiological tests and triple stimulation technique.The TST combined transcranial magnetic stimulation (TMS) of the motor cortex with peripheral collision studies.The results were expressed by the TST amplitude ratio (TST test/TST control).Based on the result of physical examination and the ratio of TST,the function of upper motor neuron was assessed.Results All of the CMT patients had typical presentations and were confirmed genetically.Hyperreflexia,Babinski sign and muscular hypertonia were

  17. Innovative quantitative testing of hand function in Charcot-Marie-Tooth neuropathy.

    Science.gov (United States)

    Alberti, Maria A; Mori, Laura; Francini, Luca; Poggi, Ilaria; Monti Bragadin, Margherita; Bellone, Emilia; Grandis, Marina; Maggi, Giovanni; Reni, Lizia; Sormani, Maria P; Tacchino, Andrea; Padua, Luca; Prada, Valeria; Bove, Marco; Schenone, Angelo

    2015-12-01

    To describe a new test to quantitatively evaluate hand function in patients affected by Charcot-Marie-Tooth neuropathy (CMT). The sensor-engineered glove test (SEGT) was applied to CMT patients (N: 26) and compared with a cohort of healthy controls (HC, N: 26). CMT patients were further divided into subjects with clinically normal (group 1) or impaired hand (group 2) function. The SEGT parameters evaluated were touch duration, inter-tapping interval, and movement rate parameters of two different sequences: finger tapping (FT) and index-medium-ring-little (IMRL) performed at self-paced mode (SPM) and maximum velocity (MV). Hand function and strength were assessed by the 9-hole peg test (9HPT) and dynamometry. Disability of patients was measured by the CMT neuropathy score. CMT patients had significantly worst performances at SEGT than controls regarding the rate of execution of both FT (at MV) and IMRL sequences (at SPM and MV). The rate parameter at MV in IMRL sequence showed a significant trend of decreasing in its average between HC (n: 26, rate = 3.08 ± 0.52 Hz), group 1 (n: 9, rate = 2.64 ± 0.66 Hz) and group 2 (n: 17, rate = 2.19 ± 0.45 Hz) (p for trend CMT neuropathy score. The SEGT test is sensitive to show hand dysfunction in CMT patients, with and without clinically impaired hands. PMID:26456943

  18. Genética de la enfermedad de Charcot-Marie-Tooth autosómica recesiva

    OpenAIRE

    Claramunt Alonso, Reyes

    2008-01-01

    RESUMEN El objetivo de esta tesis doctoral es profundizar en el conocimiento de las bases genéticas y moleculares de la enfermedad de Charcot-Marie-Tooth, especialmente de las formas con herencia autosómica recesiva. En este sentido, se incluyen los resultados obtenidos del análisis genético y molecular del gen GDAP1 en una serie de 118 familias de origen español, cuyas mutaciones son las causantes de la forma autosómica recesiva axonal tipo 4A (CMT4A), así como también, el estudio genétic...

  19. Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

    Science.gov (United States)

    Brewer, Megan H.; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P.; Ryan, Monique M.; Subramanian, Gopinath M.; Young, Helen K.; Zuchner, Stephan; Reddel, Stephen W.; Nicholson, Garth A.; Kennerson, Marina L.

    2016-01-01

    With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

  20. Clinical and Electrophysiological Studies of a Family with Probable X-linked Dominant Charcot-Marie-Tooth Neuropathy and Ptosis.

    Directory of Open Access Journals (Sweden)

    Tony Wu

    2004-07-01

    Full Text Available Background: The X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX is ahereditary motor and sensory neuropathy linked to a variety of mutations inthe connexin32 (Cx32 gene. Clinical and genetic features of CMTX havenot previously been reported in Taiwanese.Methods: Clinical evaluations and electrophysiological studies were carried out on 25family members of a Taiwanese family group. Molecular genetic analysis ofthe Cx32 gene was performed. A sural nerve biopsy was obtained from 1patient.Results: Nine patients had clinical features of X-linked dominant inheritance and amoderate Charcot-Marie-Tooth (CMT neuropathy phenotype. Moleculargenetic analysis showed no mutation of the Cx32 coding region, but revealeda G-to-A transition at position -215 of the nerve-specific promoter P2 of theCx32 gene. Ptosis is 1 clinical manifestation of neuropathy in this probableCMTX family. Familial hyperthyroidism is an additional independent featureof the family. Electrophysiological and histological studies showed featuresof axonal neuropathy. Multimodality evoked potential studies revealed normalcentral motor and sensory conduction velocities.Conclusions: The presence of ptosis in this family illustrates the existence of clinical heterogeneityamong related family members with CMTX similar to that inCMT of autosomal inheritance. Electrophysiological and histological findingsrevealed normal central conduction and axonal neuropathy.

  1. A brief review of recent Charcot-Marie-Tooth research and priorities [v1; ref status: indexed, http://f1000r.es/53g

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-02-01

    Full Text Available This brief review of current research progress on Charcot-Marie-Tooth (CMT disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases.

  2. Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A.

    Science.gov (United States)

    Kawalec, Maria; Zabłocka, Barbara; Kabzińska, Dagmara; Neska, Jacek; Beręsewicz, Małgorzata

    2014-01-01

    Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot-Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve axons. The precise mechanism by which mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is a hypothesis suggesting the involvement of reduced expression of a homologous protein, mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein expression profiles in different mouse tissues, with special attention paid to dorsal root ganglia (DRGs), as parts of the peripheral nervous system. Quantitative measurement relating to mRNA revealed that expression of the Mfn2 gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system samples and other tissues studied. This result was further supported by Western blot evaluation. Both these sets of data confirm the hypothesis that the cellular consequences of mutations in the mitofusin 2 gene can mostly be manifested in the peripheral nervous system. PMID:25574749

  3. Disease: H00264 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ease (hereditary motor sensory neuropathies) and hereditary sensory and autonomic neuropathies. Neurologist...pheral neuropathies characterized by progressive distal wasting and loss of reflexes in the muscles of the legs. Neurodegenerati...y of Charcot-Marie-Tooth disease. Neurogenetics 4:1-15 (2002) PMID:17595294 Nangle LA,...Peroneal muscular atrophy Charcot-Marie-Tooth disease is a genetically heterogeneous group of inherited peri...an V Charcot-Marie-Tooth disease: a clinico-genetic confrontation. Ann Hum Genet 72:416-41 (2008) PMID:16775

  4. Enfermedad de Charcot Marie Tooth (CMT4A por mutacion en el gen GDAP1: reporte de una familia colombiana

    Directory of Open Access Journals (Sweden)

    Angela Milena Martin

    2015-12-01

    Full Text Available Antecedentes:Las mutaciones del gen GDAP1 son causantes de la enfermedad de Charcot Marie Tooth tanto autosómica dominante como recesiva, y se han reportado más de 40 mutaciones distintas. La mutación recesiva Q163X ha sido descrita en pacientes de ascendencia española y se ha demostrado una mutación fundadora originaria de España en pacientes de origen suramericano. Describimos las características físicas e histológicas y el impacto molecular de la mutación Q163X en una familia colombiana.Objetivo:Se describe el impacto de la mutación Q163X en las características físicas, histológicas y moleculares en una familia colombiana.Métodos:Se describe dos pacientes de sexo femenino, hijas de padres consanguíneos, quienes presentaron inicio de síntomas en los dos primeros años de vida, mostrando deterioro funcional severo, sin evidencia de dismorfía, disfonía o parálisis diafragmática. Los estudios de electrofisiología mostraron una neuropatía sensitiva y motora con patrón axonal. Se solicitó la secuenciación del gen GDAP1, y el estudio identificó una mutación homocigota puntual (c. 487 C>T en el exón 4, causando un codón de parada prematuro (p. Q163X. Este resultado confirma el diagnóstico de Enfermedad de Charcot Marie Tooth, tipo 4A (recesiva, tipo axonal.Resultados:Las pacientes fueron remitidas al servicio de Fisiatría para evaluación de métodos de asistencia para deambulación. Ellas reciben seguimiento por el servicio de Neumología, quienes vigilan la función pulmonar y el desarrollo de parálisis diafragmática. Se brindó asesoramiento genético. La genealogía del paciente, las características fenotípicas y los hallazgos en los estudios electrofisiológicos son herramientas valiosas en el enfoque clínico del paciente con CMT, de forma que se pueda plantear una posible mutación causal. Se debe considerar la presencia de mutaciones en el gen GDAP1 en pacientes de origen suramericano, en especial la

  5. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  6. Fisiopatología celular del déficit de GDAP1, relacionado con la enfermedad de Charcot-Marie-Tooth

    OpenAIRE

    Pla Martín, David

    2012-01-01

    La enfermedad de Charcot-Marie-Tooth es uno de los trastornos neurológicos hereditarios más comunes que afecta aproximadamente a uno de casa 2.500 – 5.000 habitantes. La enfermedad CMT se clasifica en neuropatías desmielinizantes (CMT1) y neuropatías axonales (CMT2). Para ambas entidades se han descrito diversos patrones de herencia. Actualmente se conocen más de 40 genes implicados en la enfermedad siendo GDAP1 uno de los más variables en cuanto al fenotipo. Mutaciones en el gen GDAP1 se han...

  7. 腓骨肌萎缩症1型患者肌电图及PMP22基因特点分析%Electromyography and PMP22 gene analysis in patients with type 1 Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    潘晓丽; 潘志宏; 张楠楠; 高红

    2015-01-01

    目的:探讨和研究腓骨肌萎缩症1型(Charcot‐Marie‐Tooth disease 1,CMT1)患者肌电图和 PMP22基因改变特点。方法对43例CM T1患者进行常规神经传导速度和肌电图检查,应用PCR双酶切方法对其中33例CM T1患者及15名健康志愿者(对照组)检测17p11.2‐12 PM P22基因重复序列(即1760 bp片段)。33例CM T1患者依有无17p11.2‐12 PM P22基因特异性片段分为 PM P22基因特异性片段阳性组与阴性组,比较两组患者神经传导改变有无差异。结果43例患者均行肌电图检测,均表现为运动或感觉神经传导速度存在明显减慢(100%),感觉神经病变重于运动神经,下肢受累程度重于上肢;所检129块肌肉中,88块(68.2%)呈神经源性损害。经 PM P22基因学检测的33例中20例(60.6%)检测出1760 bp片断,对照组均未检测到此片段。PM P22基因特异性片段阳性组感觉神经传导速度、运动神经传导速度及远端潜伏期与阴性组比较差异均无统计学意义(P>0.05)。结论 CMT1患者肌电图改变具有其特异性,结合PCR‐双酶切法检测 PMP22特异性基因重复序列可提高诊断CM T1的准确性及敏感性。%Objective To study the electromyography and PM P22 gene features in patients with type 1 Charcot‐Marie‐Tooth (CMT ) disease . Methods Routine electromyography and nerve conduction were performed in 43 patients with CMT 1 .Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect PMP22 gene duplication on chromosome 17p11.2‐12 (1760 bp) in 33 CMT 1 patients and 15 healthy volunteers (the control group) .According to the presence or absence of 17 p11.2‐12 PMP22 gene segments ,33 CMT 1 patients were divided into the positive group and the negative group . Parameters of nerve conduction were compared between two groups .Results All of the patients had the nerve conduction velocities slower or disappeared

  8. Charcot-Marie-Tooth disease: The development of a diagnostic platform using next generation sequencing

    DEFF Research Database (Denmark)

    Christensen, Rikke; Væth, Signe; Thorsen, Kasper;

    sequenced on a Hiseq2000. Data analysis was performed using CLC Genomics Workbench v7.0.3. Results and Conclusion: Preliminary results indicate an increased diagnostic yield when analyzing 63 CMT associated genes compared to previous Sanger sequencing of 4 genes. The introduction of NGS in CMT diagnostics...

  9. GDAP1-related autosomal dominant Charcot-Marie-Tooth disease : phenotypical and MRI features

    OpenAIRE

    Sivera Mascaró, Rafael; Álvarez Sabin, Jose; Sevilla Mantecón, Maria Teresa

    2012-01-01

    El present estudi es basa en la descripció de quatre famílies portadores d'una mateixa mutació puntual (p.R120W) en el gen GDAP1 que segreguen d'una manera autosòmica dominant. Les trobades més rellevants foren: - Els individus afectats varen tindre un començament més tardà i un fenotipus més lleu que les mutacions recessives del gen GDAP-1, però amb una gran variabilitat clínica. - La Resonància Magnètica Muscular va demostrar una afectació selectiva de la musculatura intrínseca del peu i la...

  10. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v2; ref status: indexed, http://f1000r.es/3am

    Directory of Open Access Journals (Sweden)

    Lori Sames

    2014-04-01

    Full Text Available Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF, Hannah's Hope Fund (HHF, The Neuropathy Association (TNA and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies

  11. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v1; ref status: indexed, http://f1000r.es/33n

    Directory of Open Access Journals (Sweden)

    Lori Sames

    2014-04-01

    Full Text Available Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF, Hannah's Hope Fund (HHF, The Neuropathy Association (TNA and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies

  12. INF2 mutations associated with dominant inherited intermediate Charcot-Marie-Tooth neuropathy with focal segmental glomerulosclerosis in two Chinese patients.

    Science.gov (United States)

    Jin, Suqin; Wang, Wei; Wang, Renbin; Lv, He; Zhang, Wei; Wang, Zhaoxia; Jiao, Jinsong; Yuan, Yun

    2015-01-01

    Recently, mutations in the inverted formin 2 (INF2) gene have been indentified in patients with dominant inherited intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) with focal segmental glomerulosclerosis (FSGS). We report clinical and nerve pathological changes in two Chinese patients. Case 1 is 27 years old and presented with distal muscle weakness and atrophy of legs at the age of 13 and renal failure at the age of 26. Three of his family members died due to pure renal failure. Case 2 is 22 years old and presented with distal muscle weakness and atrophy of the legs with transient attacks of difficulty in speaking at age 17. Proteinuria was found by routine urine test at the same time. Sural nerve biopsy revealed moderate-to-severe loss of myelinated fibers with union bulbs and regeneration clusters in both patients. Ultrastructurally, numerous elongated extensions of Schwann cells of unmyelinated fibers could be seen in both patients. INF2 gene mutation screening revealed c.451 T>C in case 1 and c.341 G>A in case 2. This is the first report of Chinese patients with INF2-related DI-CMT. The c.451 T>C mutant was responsible for both isolated FSGS and a dual phenotype of FSGS and neuropathy within one family. Intrafamilial variability can be found with the same INF2 mutation. The CNS manifestations further broadened the clinical spectrum of INF2- associated disorders. PMID:25943269

  13. Tolerability and efficacy study of P2X7 inhibition in experimental Charcot-Marie-Tooth type 1A (CMT1A) neuropathy.

    Science.gov (United States)

    Sociali, Giovanna; Visigalli, Davide; Prukop, Thomas; Cervellini, Ilaria; Mannino, Elena; Venturi, Consuelo; Bruzzone, Santina; Sereda, Michael W; Schenone, Angelo

    2016-11-01

    Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy for which pharmacological treatments are not yet available. An abnormally high intracellular Ca(2+) concentration was observed in Schwann cells (SC) from CMT1A rats, caused by the PMP22-mediated overexpression of the P2X7 purinoceptor. The purpose of this study was to investigate the tolerability and therapeutic potential of a pharmacological antagonist of the P2X7 receptor (A438079) in CMT1A. A438079 ameliorated in vitro myelination of organotypic DRG cultures from CMT1A rats. Furthermore, we performed an experimental therapeutic trial in PMP22 transgenic and in wild-type rats. A preliminary dose-escalation trial showed that 3mg/kg A438079 administered via intraperitoneal injection every 24h for four weeks was well tolerated by wild type and CMT1A rats. Affected rats treated with 3mg/kg A438079 revealed a significant improvement of the muscle strength, when compared to placebo controls. Importantly, histologic analysis revealed a significant increase of the total number of myelinated axons in tibial nerves. Moreover, a significant decrease of the hypermyelination of small caliber axons and a significant increase of the frequency and diameter of large caliber myelinated axons was highlighted. An improved distal motor latencies was recorded, whereas compound muscle action potentials (CMAP) remained unaltered. A438079 reduced the SC differentiation defect in CMT1A rats. These results show that pharmacological inhibition of the P2X7 receptor is well tolerated in CMT1A rats and represents a proof-of-principle that antagonizing this pathway may correct the molecular derangements and improve the clinical phenotype in the CMT1A neuropathy. PMID:27431093

  14.  Hypertelorism in Charcot-Marie-Tooth disease 1A from the common PMP22 duplication: A Case Report

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2012-03-01

    Full Text Available  The 1.4Mb tandem-duplication in the PMP22 gene at 17p11.2 usually manifests as hereditary sensorimotor polyneuropathy with foot deformity, sensorineural hearing-loss, moderate developmental delay, and gait disturbance. Hypertelorism and marked phenotypic variability within a single family has not been reported. In a single family, the PMP22 tandem-duplication manifested as short stature, sensorimotor polyneuropathy, tremor, ataxia, sensorineural hearing-loss, and hypothyroidism in the 27 years-old index case, as mild facial dysmorphism, muscle cramps, tinnitus, intention tremor, bradydiadochokinesia, and sensorimotor polyneuropathy in the 31 year-old half-brother of the index-patient, and as sensorimotor polyneuropathy and foot deformityin the father of the two. The half-brother additionally presented with hypertelorism, not previously reported in PMP22tandem-duplication carriers. The presented cases show that the tandem-duplication 17p11.2 may present with marked intra-familialphenotype variability and that mild facial dysmorphism with stuck-out ears and hypertelorism may be a rare phenotypic feature of this mutation. The causal relation between facial dysmorphism and the PMP22 tandem-duplication, however, remains speculative.

  15. Is the extracellular ATP a key in X-linked Charcot-Marie-Tooth disease and in inherited non-syndromic deafness?

    OpenAIRE

    Mas del Molino, Ezequiel

    2011-01-01

    [spa] El ATP es una molécula ampliamente conocida por su papel en muchas funciones como la homeostasis celular, el mantenimiento de gradientes iónicos, el mantenimiento del pH en gránulos secretores, el almacenamiento energético, regulador de la interacción actina-miosina, etc. Además, el ATP puede actuar como molécula señalizadora a través de los receptores purinérgicos P2. De receptores P2 hay de dos tipos, los P2X, que son ionotrópicos, y los P2Y que son metabotrópicos. Los primeros son un...

  16. 腓骨肌萎缩症X型伴有可逆性中枢神统系统受累%Charcot Marie Tooth type X with reversible central nerve system disorders

    Institute of Scientific and Technical Information of China (English)

    张洁; 孔双艳; 杨琼; 邢岩

    2016-01-01

    目的:探讨的腓骨肌萎缩症X型的临床特点和引起中枢神经系统受累可能的发病机制。方法报道1例国内未报道过的CMTX可引起中枢神经系统受累Cx32基因突变,分析该例患者的临床、电生理及病理改变特点。结果该患者为基因检查确诊Arg424Trp( R142W)突变的CMTX。临床存在可逆性眼震,电生理提示感觉运动神经受累均受累,轴索髓鞘均损害。肌肉活检提示慢性神经源性病理改变。周围神经活检示周围神经髓鞘损害为主。 BAEP提示可逆性中枢性损害。结论 R142W突变的CMTX可以在应激条件下出现可逆性中枢神经系统损害。%Objective To investigate the clinical features of Charcot Marie Tooth X ( CMTX) and possible pathogenesis of central nervous system involved.Methods Cx32 gene mutations in 1 cases of with central nervous system disorded were reported, and the clinical, electrophysiological and pathological characteristics of the patient was analyzed retrospectively.Results The Arg424Trp(R142W) mutation of the CMTX gene was confirmed.The clinical presence of reversible nystagmus, electrophysiological prompt sensory and motor nerve were involed with axonal myelin damage.Muscle biopsy indicated that the chronic axonal peripheral nerve pathological changes.BAEP indicated that the reversibility of the central nervous system damage.Conclusion The R142W mutation of CMTX can appear to be reversible central nervous system damage under the stress conditions.

  17. Molecular genetics of neurodegenerative diseases.

    Science.gov (United States)

    Roses, A D

    1993-02-01

    Recent progress in human neurogenetics has led to the discovery of new modes of inheritance and disease expression, including 1) stably inherited duplications in Charcot-Marie-Tooth disease type 1a, 2) dynamic mutations in fragile X syndrome and myotonic dystrophy, and 3) identical mutations with different phenotypes in fatal familial insomnia and Creutzfeldt-Jakob disease. The mechanisms by which known mutations of the amyloid precursor protein lead to early-onset Alzheimer's disease remain unexplained, despite hundreds of recent studies of beta-amyloid. PMID:8428064

  18. Musculoskeletal complications of neuromuscular disease in children.

    Science.gov (United States)

    Driscoll, Sherilyn W; Skinner, Joline

    2008-02-01

    A wide variety of neuromuscular diseases affect children, including central nervous system disorders such as cerebral palsy and spinal cord injury; motor neuron disorders such as spinal muscular atrophy; peripheral nerve disorders such as Charcot-Marie-Tooth disease; neuromuscular junction disorders such as congenital myasthenia gravis; and muscle fiber disorders such as Duchenne's muscular dystrophy. Although the origins and clinical syndromes vary significantly, outcomes related to musculoskeletal complications are often shared. The most frequently encountered musculoskeletal complications of neuromuscular disorders in children are scoliosis, bony rotational deformities, and hip dysplasia. Management is often challenging to those who work with children who have neuromuscular disorders. PMID:18194756

  19. Decreased Variability of the 6-Minute Walk Test by Heart Rate Correction in Patients with Neuromuscular Disease

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Witting, Nanna; Vissing, John

    2014-01-01

    by heart rate correction. METHODS: Sixteen patients with neuromuscular diseases, including Facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, Charcot-Marie-Tooths, Dystrophia Myotonica and Congenital Myopathy and 12 healthy subjects were studied. Patients were excluded if they...... had cardiac arrhythmias, if they received drug treatment for hypertension or any other medical conditions that could interfere with the interpretation of the heart rate and walking capability. All completed three 6-minute walk tests on three different test-days. Heart rate was measured continuously...... treatment trials....

  20. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  1. 神经超声在Chacot-Marie-Tooth1型和慢性炎性脱髓鞘性多发性神经根神经病鉴别诊断中的价值%The utility of peripheral nerve ultrasound in differentiating Charcot-Marie-Tooth type 1 from chronic inflammatory demyelinating polyradiculoneuropathy

    Institute of Scientific and Technical Information of China (English)

    刘明生; 牛婧雯; 李亦; 吴双; 管宇宙; 崔丽英

    2016-01-01

    CharcotMarie-Tooth type 1 (CMT1) from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Methods Eighteen patients with CIDP,13 patients with CMT1 and 16 healthy controls were recruited prospectively from Peking Union Medical College Hospital between January 2014 and July 2015 for this study.Ultrasonographic tests were performed via nerve tracing from wrist to axilla on median and ulnar nerve with a 10 MHz linear array probe.The cross sectional areas (CSAs) were measured at 10 defined sites of the nerves,respectively.Results CSAs (mm2) at all sites of median nerve were significantly increased in CMT1 than in CIDP (10.5 ±5.3 vs7.8 ±2.4,10.9 ±3.6 vs 6.8 ±1.9,11.5 ±5.0 vs7.3 ±1.8,13.5 ± 4.4vs7.2±2.5,16.0±4.5vs7.2±2.1,17.1±5.1vs7.0±2.8,21.0±4.5vs9.5±4.8,24.3±6.9 vs 9.5 ±4.3,23.9 ±6.0 vs 10.2 ±4.3,22.4 ±6.7 vs 9.8 ±2.1;t=2.141,4.766,2.935,4.858,6.715,6.602,7.148,7.100,8.078,6.498,respectively,all P < 0.05).CSAs (mm2) at all sites of ulnar nerve were significantly increased in CMT1 than in CIDP (7.9 ± 1.8 vs 4.0 ± 1.3,8.9 ± 2.0 vs 4.9 ± 1.3,13.5±1.9 vs6.5±2.4,15.0±4.3 vs 6.5 ±1.5,15.8 ±4.4 vs 6.8 ±3.3,11.6±2.3 vs6.9± 3.1,10.2±3.2vs7.6±2.8,14.0±3.0vs6.6±2.1,19.2±3.7vs7.6±4.4,18.1±3.6vs6.3± 2.5;t =7.652,7.414,9.194,6.893,6.443,4.766,2.561,7.897,8.113,11.554,respectively,all P < 0.05).CSAs at 8 sites of median nerve and 8 sites of ulnar nerve were significantly increased in CIDP than in healthy controls.Receiver operation characteristic curve analysis revealed that CSA was suited for differentiating CMT1 from CIDP,and the area under curve in 8 sites of median nerve and 9 sites in ulnar nerve was more than 0.9.Conclusions CSAs measured at different sites by peripheral nerve ultrasound in CMT1 were significantly increased than in CIDP.Measurement of CSAs by peripheral nerve ultrasound can be used for differentiating CMTI from CIDP.

  2. Disease: H00929 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00929 Congenital vertical talus Congenital vertical talus is a primary dislocation... Gurnett CA, Connolly AM, Pestronk A, Dobbs MB Skeletal muscle abnormalities and genetic factors related to vertical...on, gene) Levinsohn EM, Shrimpton AE, Cady RB, Packard DS, Hootnick DR Congenital vertical talus in four gen...otnick DR A HOX gene mutation in a family with isolated congenital vertical talus and Charcot-Marie-Tooth disease. Am J Hum Genet 75:92-6 (2004) PMID:16450407 (description, gene) Dobbs MB, Gurnett CA, Pierce B, Exner GU, Robarge J, Morcuende JA, Cole WG, Templeton PA, Foster B, Bowcock AM HOXD10 M319K mutation in a family with isolated congenital vertical talus. J Orthop Res 24:448-53 (2006) ...

  3. The impact of autophagy on peripheral synapses in health and disease.

    Science.gov (United States)

    Rudolf, Rudiger; Khan, Muzamil Majid; Wild, Franziska; Hashemolhosseini, Said

    2016-01-01

    Alterations of autophagy have been linked to several peripheral nervous system diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. Modulation of autophagy by metabolic or pharmacological interventions has been increasingly recognized as a strategy to fight many of these disorders. Cellular processes that are aberrant in case of impaired autophagy and that might lead to these diseases belong to three different categories: (1) clearing of protein aggregates, (2) regulation of vesicle and cargo turnover, and (3) disposal of damaged mitochondria. This review summarizes the present literature that addresses both, the impact and mechanisms of autophagy on the health of the peripheral nervous system and treatment proposals for human disorders associated with impaired autophagy. PMID:27100517

  4. A Charcot-Marie-Tooth disease resembling to chronic inflammatory demyelinating polyradiculoneuropathy: a report of two cases%慢性炎性脱髓鞘性周围神经病样表现的腓骨肌萎缩症二例

    Institute of Scientific and Technical Information of China (English)

    王毅; 乔凯; 吕传真

    2005-01-01

    目的观察亚急性病程的慢性炎性脱髓鞘性周围神经病(CIDP)样表现的腓骨肌萎缩症(CMT)的临床、病理和电生理特点.方法报道2例亚急性的CIDP样表现的CMT患者的临床、神经电生理及周围神经活检的病理特点.结果 2例证实为17p12重复突变的CMT1A患者,慢性病程中亚急性加重,临床表现类似于CIDP.肌电图示运动神经传导速度(MNCV)减慢、阻滞;神经活检见洋葱头样改变,髓鞘脱失,有炎性细胞的浸润,证明有炎性脱髓鞘的CMT1A存在,且免疫治疗有效.结论慢性病程的CMT1A可有类似于CIDP的病程和临床表现,免疫治疗可改善症状.

  5. Polymyositis: Diagnosis

    Science.gov (United States)

    ... Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease (CMT) Congenital muscular dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) ... examination. This may be followed by some lab tests, perhaps of the electrical activity inside the muscles ...

  6. Inclusion-Body Myositis: Diagnosis

    Science.gov (United States)

    ... Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease (CMT) Congenital muscular dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) ... examination. This may be followed by some lab tests, perhaps of the electrical activity inside the muscles. ...

  7. Dermatomyositis: Diagnosis

    Science.gov (United States)

    ... Amyotrophic Lateral Sclerosis (ALS) Charcot-Marie-Tooth Disease (CMT) Congenital muscular dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) ... examination. This may be followed by some lab tests, perhaps of the electrical activity inside the muscles, ...

  8. Mitochondrial Fusion Proteins and Human Diseases

    Directory of Open Access Journals (Sweden)

    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  9. 'Laminopathies': A wide spectrum of human diseases

    International Nuclear Information System (INIS)

    Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called 'laminopathies.' Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasia and Pelger-Huet anomaly. While mutations and clinical phenotypes of 'laminopathies' have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new 'laminopathies' and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies

  10. The regulation of fine movements in patients with Charcot Marie Tooth, type Ia : Some ideas about continuous adaptation

    NARCIS (Netherlands)

    Mulder, T.; Den Otter, R.; van Engelen, B.

    2001-01-01

    The flexibility of the human motor system is remarkable. Even when parts of the system are damaged, the output often remains optimal or near-optimal. The neuromotor system is designed to keep the output optimal by shifting between input sources. This capability is termed the principle of continuous

  11. Lamin A/C truncation in dilated cardiomyopathy with conduction disease

    Directory of Open Access Journals (Sweden)

    Huber Jill M

    2003-07-01

    Full Text Available Abstract Background Mutations in the gene encoding the nuclear membrane protein lamin A/C have been associated with at least 7 distinct diseases including autosomal dominant dilated cardiomyopathy with conduction system disease, autosomal dominant and recessive Emery Dreifuss Muscular Dystrophy, limb girdle muscular dystrophy type 1B, autosomal recessive type 2 Charcot Marie Tooth, mandibuloacral dysplasia, familial partial lipodystrophy and Hutchinson-Gilford progeria. Methods We used mutation detection to evaluate the lamin A/C gene in a 45 year-old woman with familial dilated cardiomyopathy and conduction system disease whose family has been well characterized for this phenotype 1. Results DNA from the proband was analyzed, and a novel 2 base-pair deletion c.908_909delCT in LMNA was identified. Conclusions Mutations in the gene encoding lamin A/C can lead to significant cardiac conduction system disease that can be successfully treated with pacemakers and/or defibrillators. Genetic screening can help assess risk for arrhythmia and need for device implantation.

  12. Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases

    Science.gov (United States)

    Heidari, Moones; Gerami, Sam H.; Bassett, Brianna; Graham, Ross M.; Chua, Anita C.G.; Aryal, Ritambhara; House, Michael J.; Collingwood, Joanna F.; Bettencourt, Conceição; Houlden, Henry; Ryten, Mina; Olynyk, John K.; Trinder, Debbie; Johnstone, Daniel M.; Milward, Elizabeth A.

    2016-01-01

    ABSTRACT We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe−/−xTfr2mut mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family ‘neurodegeneration with brain iron accumulation’ (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading. Concordance between the mouse transcriptome changes and human myelin-related gene expression networks in normal and NBIA basal ganglia testifies to potential clinical relevance. These analyses implicate, among others, genes linked to various rare central hypomyelinating leukodystrophies and peripheral neuropathies including Pelizaeus-Merzbacher-like disease and Charcot-Marie-Tooth disease as well as genes linked to other rare neurological diseases such as Niemann-Pick disease. The findings may help understand interrelationships of iron and myelin in more common conditions such as hemochromatosis, multiple sclerosis and various psychiatric disorders. PMID:27500074

  13. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases

    Science.gov (United States)

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K.; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C.; Idol, Jennifer; Pretorius, Pamela R.; Beirl, Alisha; Schimmenti, Lisa A.; Kindt, Katie S.; Sood, Raman; Burgess, Shawn M.

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  14. A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

    1996-07-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

  15. Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms with the RNA helicase Ddx20 (gemin3)

    NARCIS (Netherlands)

    Sun, Xiankui; Fontaine, Jean-Marc; Hoppe, Adam D.; Carra, Serena; DeGuzman, Cheryl; Martin, Jody L.; Simon, Stephanie; Vicart, Patrick; Welsh, Michael J.; Landry, Jacques; Benndorf, Rainer

    2010-01-01

    A number of missense mutations in the two related small heat shock proteins HspB8 (Hsp22) and HspB1 (Hsp27) have been associated with the inherited motor neuron diseases (MND) distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. HspB8 and HspB1 interact with each other, suggesting tha

  16. Comparison of CMT1A and CMT2: similarities and differences

    NARCIS (Netherlands)

    H.M.E. Bienfait; C. Verhamme; I.N. van Schaik; J.H.T.M. Koelman; B.W.O. de Visser; R.J. de Haan; F. Baas; B.G.M. van Engelen; M. de Visser

    2006-01-01

    To evaluate the clinical and electrophysiological similarities and differences between two large groups of patients with Charcot-Marie-Tooth disease, i.e. CMT1A and CMT2, we performed a post hoc comparison of clinical and electrophysiological data. Most CMT1A and CMT2 patients had the classical CMT

  17. Comparison of CMT1A and CMT2: similarities and differences.

    NARCIS (Netherlands)

    Bienfait, H.M.; Verhamme, C.; Schaik, I.N. van; Koelman, J.H.; Visser, B.W. de; Haan, R.J. de; Baas, F.; Engelen, B.G.M. van; Visser, M. de

    2006-01-01

    To evaluate the clinical and electrophysiological similarities and differences between two large groups of patients with Charcot-Marie-Tooth disease, i.e. CMT1A and CMT2, we performed a post hoc comparison of clinical and electrophysiological data.Most CMT1A and CMT2 patients had the classical CMT p

  18. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, S.; Lewis, P.D. (Royal Postgraduate Medical School, London (UK))

    1983-12-01

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed.

  19. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle

    International Nuclear Information System (INIS)

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed. (author)

  20. Studies of cellular radiosensitivity in hereditary disorders of nervous system and muscle.

    OpenAIRE

    Brennan, S; Lewis, P.D.

    1983-01-01

    Skin fibroblasts from patients with familial dysautonomia, Duchenne muscular dystrophy and Charcot-Marie-Tooth disease show normal sensitivity to ionising radiation, as measured by post-irradiation clonal growth. Previous reports of cellular hypersensitivity to ionising radiation and other DNA-damaging agents in familial dysautonomia and Duchenne muscular dystrophy have not been confirmed.

  1. Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.

    Science.gov (United States)

    Sanmaneechai, Oranee; Feely, Shawna; Scherer, Steven S; Herrmann, David N; Burns, Joshua; Muntoni, Francesco; Li, Jun; Siskind, Carly E; Day, John W; Laura, Matilde; Sumner, Charlotte J; Lloyd, Thomas E; Ramchandren, Sindhu; Shy, Rosemary R; Grider, Tiffany; Bacon, Chelsea; Finkel, Richard S; Yum, Sabrina W; Moroni, Isabella; Piscosquito, Giuseppe; Pareyson, Davide; Reilly, Mary M; Shy, Michael E

    2015-11-01

    We aimed to characterize genotype-phenotype correlations and establish baseline clinical data for peripheral neuropathies caused by mutations in the myelin protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot-Marie-Tooth disease type 1. Recent research makes clinical trials for patients with MPZ mutations a realistic possibility. However, the clinical severity varies with different mutations and natural history data on progression is sparse. We present cross-sectional data to begin to define the phenotypic spectrum and clinical baseline of patients with these mutations. A cohort of patients with MPZ gene mutations was identified in 13 centres of the Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009 and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments. Genetic testing was performed in all patients and/or in first- or second-degree relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie-Tooth disease type 1B. There were 103 patients from 71 families with 47 different MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and mutations were separated into infantile, childhood and adult-onset groups. The infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and slower nerve conductions than the other groups, and severity increased with age. Twenty-three patients had no family history of Charcot-Marie-Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking assistance or support, and 10 required wheelchairs. There was hearing loss in 21 and scoliosis in 17. Forty-two patients did not begin walking until after 15 months of age. Half of the infantile onset patients then required ambulation aids or wheelchairs for

  2. Exome sequencing resolves apparent incidental findings and reveals further complexity of SH3TC2 variant alleles causing Charcot-Marie-Tooth neuropathy

    OpenAIRE

    Lupski, James R.; Gonzaga-Jauregui, Claudia; Yang, Yaping; Bainbridge, Matthew N.; Jhangiani, Shalini; Buhay, Christian J.; Christie L Kovar; Wang, Min; Hawes, Alicia C.; Reid, Jeffrey G; Eng, Christine; Muzny, Donna M.; Gibbs, Richard A.

    2013-01-01

    Background The debate regarding the relative merits of whole genome sequencing (WGS) versus exome sequencing (ES) centers around comparative cost, average depth of coverage for each interrogated base, and their relative efficiency in the identification of medically actionable variants from the myriad of variants identified by each approach. Nevertheless, few genomes have been subjected to both WGS and ES, using multiple next generation sequencing platforms. In addition, no personal genome has...

  3. Organization experience of diagnostic and medicosocial services for patients with Charcot—Marie—Tooth disease in Krasnoyarsk region

    Directory of Open Access Journals (Sweden)

    E. V. Glushchenko

    2012-01-01

    Full Text Available Hereditary neuropathy Charcot-Marie-Tooth (CMT is the most common form of hereditary polyneuropathies. Goal of the study was the development of evidence-based diagnostic and treatment algorithms using patients with CMT (for example, in Krasnoyarsk Territory.Materials and methods: A total of 324 people. (probands and their relatives 1 and 2 lines of kinship. We analyzed 125 (38,5 % clinical cases of CMT, 64/125 (51,2 % clinical cases were include to statistical analysis (probands and their family trees, past the full range of clinical and laboratory findings according to the protocol this study. Age ranged from 6 to 81 years, median age — 30,5 years, including women 24 (37,5 %, median age — 33,5 years; males 40 (62,5 %, median age — 28,5 years. Methods of diagnosis: clinical, genetic, neurophysiological, molecular genetic, assessment of quality of life assessment of anxiety and depression.Results: The family history of CMT noted in 53/57 (93,0 % cases, with a predominance of autosomal dominant type of inheritance —52 (91,2 % cases. As a result of DNA testing duplication of peripheral myelin protein gene (RMR22 on chromosome 17, held 34 survey, this mutation was found in 17 (50,0 % patients. Modified method of computer esthesiometry for CMT diagnosis using domestic diagnostic equipment “Vibrotester-MBN” BT-02-1 has a high sensitivity in the early stages of the disease and can be recommended for more widespread adoption of on par with other subjects of the Russian Federation.

  4. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    OpenAIRE

    Wang Yi; Pan Yan; Price Ann; Martin Lee J

    2011-01-01

    Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive ...

  5. Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy

    OpenAIRE

    Tucci,A; Liu, Y. T.; Preza, E; Pitceathly, R. D.; Chalasani, A.; Plagnol, V.; Land, J. M.; Trabzuni, D.; Ryten, M.; Jaunmuktane, Z.; Reilly, M.M.; Brandner, S; Hargreaves, I.; Hardy, J.; Singleton, A B

    2013-01-01

    Objective Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylp...

  6. A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy.

    OpenAIRE

    Cord Drögemüller; Doreen Becker; Barbara Kessler; Elisabeth Kemter; Jens Tetens; Konrad Jurina; Karin Hultin Jäderlund; Annette Flagstad; Michele Perloski; Kerstin Lindblad-Toh; Kaspar Matiasek

    2010-01-01

    The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre tea...

  7. Mechanisms for Nonrecurrent Genomic Rearrangements Associated with CMT1A or HNPP: Rare CNVs as a Cause for Missing Heritability

    OpenAIRE

    Zhang, Feng; Seeman, Pavel; Liu, Pengfei; Weterman, Marian A.J.; Gonzaga-Jauregui, Claudia; Towne, Charles F.; Batish, Sat Dev; De Vriendt, Els; De Jonghe, Peter; Rautenstrauss, Bernd; Krause, Klaus-Henning; Khajavi, Mehrdad; Posadka, Jan; Vandenberghe, Antoon; Palau, Francesc

    2010-01-01

    Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed that >99% of these rearrangements are recurrent and mediated by nonallelic homologous recombination (NAHR). Rare copy number variations (CNVs) generated by nonrecurrent rearrangeme...

  8. The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test

    OpenAIRE

    Boizot, Alexia; Talmat-Amar, Yasmina; Morrogh, Deborah; Kuntz, Nancy; Halbert, Cecile; Chabrol, Brigitte; Houlden, Henry; Stojkovic, Tanya; Schulman, Brenda; Rautenstrauss, Bernd; Bomont, Pascale

    2014-01-01

    International audience BACKGROUND: The BTB-KELCH protein Gigaxonin plays key roles in sustaining neuron survival and cytoskeleton architecture. Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network. Growing evidences suggest that GAN is a continuum with the peripheral neuropathy Charcot-Marie-Tooth diseases type 2 (CMT2). Sharing similar...

  9. Neuropathic Pain Model of Peripheral Neuropathies Mediated by Mutations of Glycyl-tRNA Synthetase

    OpenAIRE

    Lee, Seo Jin; Seo, Ah Jung; Park, Byung Sun; Jo, Hyun Woo; Huh, Youngbuhm

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using a...

  10. A Clinical Analysis of 36 Nervous System Disease Patients Acompanying Auditory Neuropathy%伴发神经系统疾病的听神经病36例临床分析

    Institute of Scientific and Technical Information of China (English)

    王锦玲; 王剑; 石力; 薛飞; 吴保仁; 高磊; 谢娟; 韩丽萍

    2011-01-01

    目的 分析一组神经系统疾病伴听神经病(auditory neuropathy,AN)患者的临床特点及两者间的关系.方法 回顾性分析36例神经系统疾病伴AN患者的临床资料,并报告10例典型病例.结果 36例伴发AN患者的神经系统疾病包括:弗雷德赖希(Friedreich)共济失调5例,腓骨肌萎缩症(charcot- marie- tooth,CMT病)4例,植烷酸储积病(Refsum病)1例,视神经萎缩9例,下肢周围神经病9例,多发性硬化2例,慢性炎症性脱髓鞘性多发性神经病(CIDP)1例,脊髓亚急性联合变性2例,运动神经元病1例,缺血缺氧性脑病1例,红斑性肢痛症1例,其中23例同时伴发其他1种或2种神经系统疾病.本组患者中14例(38.89%)首先出现双下肢无力、走路不稳、行走困难或视力减退,其余22例(61.11%)为首先出现听力减退,辨不清说话;有行走困难及耳聋家族史5例,视力减退家族史2例,新生儿黄疸史1例.神经系统检查:14例视诱发电位出现视觉径路传导障碍,16例胫神经运动传导速度减慢(12-30m/s)和/或潜伏期延长(4.1-5.8ms),6例腓肠神经感觉传导速度减慢(0-35m/s)及/或5例波幅下降(0-0.85μV);颞骨HRCT及MRI多未见异常;冷热试验26例中半规管麻痹14例;前庭诱发肌源性电位(VEMP)检测13例中9例未引出,引出的4例均幅值降低,2例潜伏期延长;纯音听力图呈低频上升型37耳(54.41%,37/68);听力损失呈中重、重及极重度共47耳(69.12%,47/68);言语识别率不成比例差于纯音听阈;ABR自波I起均未引出;DPOAE除个别频率外,全部可引出.结论 AN可伴发于多种神经系统疾病,多为周围性、遗传性神经病,多表现为下肢无力、行走困难、听话不清或视力减退一组综合征,听力障碍在病程中可先后出现,听力检测呈现AN的听力学特征,影响原发神经系统疾病的病理过程也可能影响听神经.%Objective To analyze the clinical features of nervous system disease patients with auditory

  11. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    International Nuclear Information System (INIS)

    Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions. (orig.)

  12. Non-radioactive detection of 17p11.2 duplication in CMT1A: a study of 78 patients.

    OpenAIRE

    Schiavon, F; Mostacciuolo, M. L.; Saad, F.; Merlini, L.; Siciliano, G; Angelini, C.; Danieli, G A

    1994-01-01

    Charcot-Marie-Tooth disease type 1 (CMT1) is a peripheral neuropathy characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity, mostly inherited as an autosomal dominant trait. The most common form, type 1A, is associated with a 1.5Mb DNA duplication in region p11.2-p12 of chromosome 17 in many patients. In this study a non-radioactive test for detection of the CMT1A duplication based on an RM11-GT microsatellite polymorphism is pr...

  13. Sciatic nerve tumor and tumor-like lesions - uncommon pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Wadhwa, Vibhor; Thakkar, Rashmi S.; Carrino, John A.; Chhabra, Avneesh [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Maragakis, Nicholas; Hoeke, Ahmet; Sumner, Charlotte J.; Lloyd, Thomas E. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States); Belzberg, Allan J. [Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, MD (United States)

    2012-07-15

    Sciatic nerve mass-like enlargement caused by peripheral nerve sheath tumors or neurocutaneous syndromes such as neurofibromatosis or schwannomatosis has been widely reported. Other causes of enlargement, such as from perineuroma, fibromatosis, neurolymphoma, amyloidosis, endometriosis, intraneural ganglion cyst, Charcot-Marie-Tooth disease, and chronic inflammatory demyelinating polyneuropathy are relatively rare. High-resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss normal anatomy of the sciatic nerve and MRI findings of the above-mentioned lesions. (orig.)

  14. Clinical and Genetic Characteristics Analysis of Auditory Neuropathy Acompanying Peripheral Nervous System Disease%以听神经病为首发病伴周围神经病家系的听力学及遗传学特征分析

    Institute of Scientific and Technical Information of China (English)

    齐悦; 兰兰; 史伟; 张秋静; 纵亮; 李娜; 王大勇; 李倩; 王秋菊

    2012-01-01

    目的 分析以听神经病为首发病伴周围神经病家系的临床听力学及遗传学特征.方法 对3个以听神经病为首发病伴周围神经病的家系进行病史采集、专科体检、听力学检查及相关的神经系统检查,从患者的临床表型、听力学检测、家系谱图及家系遗传学特征进行分析.结果 3个家系中的患者均以听神经病为首发病,其中,2个家系中的患者伴发Charcot-Marie-Tooth(CMT)综合征、1个家系中的患者伴发运动神经元病.3个家系中患者的表型特点均为青少年期发病的低频下降为主的双侧感音神经性聋,多伴局部感觉及运动障碍.家系谱分析显示两个伴发CMT综合征家系分别具有常染色体隐性及X连锁隐性遗传特征,而伴发运动神经元病家系则表现出常染色体隐性遗传特征.结论 部分听神经病可表现为周围神经病的首发病,青少年期发病,双耳低频下降型感音神经性聋;具有为常染色体隐性或X连锁隐性遗传特征.%Objective To analysis the clinical and genetic characteristics of three Chinese families with auditory neuropathy and peripheral nervous system disease. Methods The three Chinese families with auditory neuropathy and peripheral nervous system disease were investigated by history collectioning, physical examinationing, audiologi-cal examinationing and drawing the family trees. The systematic examination of audiology including audiological examination, such as pure tone testing, OAE, ABR,and neurologic examination. Results The three families had been diagnosed with bilateral sensorineural hearing loss mainly at low frequency. The hearing loss ranged from mild to serves. Patients all had tinnitus, sensory and movement disorders, partly had ataxia, optic atrophy and other symptoms. Among them, seven of the eight patients accepted systematic examination of audiology. All the audiological diagnostic results showed typical characters of auditory neuropathy

  15. Connexin: a potential novel target for protecting the central nervous system?

    Directory of Open Access Journals (Sweden)

    Hong-yan Xie

    2015-01-01

    Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

  16. Connexin:a potential novel target for protecting the central nervous system?

    Institute of Scientific and Technical Information of China (English)

    Hong-yan Xie; Yu Cui; Fang Deng; Jia-chun Feng

    2015-01-01

    Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings re-garding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer’s disease, Parkinson’s disease, X-linked Charcot-Marie-Tooth disease, Peli-zaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

  17. The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders.

    Science.gov (United States)

    Eira, Jessica; Silva, Catarina Santos; Sousa, Mónica Mendes; Liz, Márcia Almeida

    2016-06-01

    Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease. PMID:27095262

  18. Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy

    Directory of Open Access Journals (Sweden)

    Claudia Gonzaga-Jauregui

    2015-08-01

    Full Text Available Charcot-Marie-Tooth (CMT disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37 of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.

  19. Genetic disorders producing compressive radiculopathy.

    Science.gov (United States)

    Corey, Joseph M

    2006-11-01

    Back pain is a frequent complaint seen in neurological practice. In evaluating back pain, neurologists are asked to evaluate patients for radiculopathy, determine whether they may benefit from surgery, and help guide management. Although disc herniation is the most common etiology of compressive radiculopathy, there are many other causes, including genetic disorders. This article is a discussion of genetic disorders that cause or contribute to radiculopathies. These genetic disorders include neurofibromatosis, Paget's disease of bone, and ankylosing spondylitis. Numerous genetic disorders can also lead to deformities of the spine, including spinal muscular atrophy, Friedreich's ataxia, Charcot-Marie-Tooth disease, familial dysautonomia, idiopathic torsional dystonia, Marfan's syndrome, and Ehlers-Danlos syndrome. However, the extent of radiculopathy caused by spine deformities is essentially absent from the literature. Finally, recent investigation into the heritability of disc degeneration and lumbar disc herniation suggests a significant genetic component in the etiology of lumbar disc disease. PMID:17048153

  20. The proteolipid protein gene: Double, double, . . . and trouble

    Energy Technology Data Exchange (ETDEWEB)

    Hodes, M.E.; Dlouhy, S.R. [Indiana Univ. School of Medicine, Indianapolis, IN (United States)

    1996-07-01

    That more of a good thing may be too much has been apparent at least since the discovery that Down syndrome is caused by three copies of chromosome 21 instead of the normal two. Duplications of myelin genes also lead to trouble. An extra dose of PMP22, the gene for a protein of peripheral nervous system myelin, causes Charcot-Marie Tooth type 1A disease (CMT1A). Increased dosage of the proteolipid protein gene, PLP, which encodes the chief protein of CNS myelin, can cause Pelizaeus-Merzbacher disease (PMD). The work of Inoue et al. is of particular importance because they found the duplication in four of five families with {open_quotes}classical{close_quotes} PMD, whereas other changes in PLP, such as missense mutations, are found in no more than one in four or five patients with the disease. 27 refs.

  1. Intracellular transport proteins: classification, structure and function of kinesins

    Directory of Open Access Journals (Sweden)

    Agnieszka Chudy

    2011-09-01

    Full Text Available Correct cell functioning, division and morphogenesis rely on efficient intracellular transport. Apart from dyneins and myosins, kinesins are the main proteins responsible for intracellular movement. Kinesins are a large, diverse group of motor proteins, which based on phylogenetic similarity were classified into fourteen families. Among these families, due to the location of their motor domains, three groups have been characterized: N-, C- and M-kinesin. As molecular motors, kinesins transport various molecules and vesicles mainly towards the microtubule plus end (from the cell body participating in anterograde transport, although there are also kinesins involved in retrograde transport (C-kinesins. Kinesins are also involved in spindle formation, chromosome segregation, and spermatogenesis. Because of their great importance for the correct functioning of cells, mutations in kinesin coding genes may lead to such neurodegenerative diseases as dominant hereditary spastic paraplegia or Charcot-Marie-Tooth disease.

  2. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction

    Directory of Open Access Journals (Sweden)

    Antonio eZorzano

    2015-06-01

    Full Text Available Mitochondrial dynamics is a term that encompasses the movement of mitochondria along the cytoskeleton, regulation of their architecture, and connectivity mediated by tethering and fusion/fission. The importance of these events in cell physiology and pathology has been partially unraveled with the identification of the genes responsible for the catalysis of mitochondrial fusion and fission. Mutations in two mitochondrial fusion genes (MFN2 and OPA1 cause neurodegenerative diseases, namely Charcot-Marie Tooth type 2A and autosomal dominant optic atrophy. Alterations in mitochondrial dynamics may be involved in the pathophysiology of prevalent neurodegenerative conditions. Moreover, impairment of the activity of mitochondrial fusion proteins dysregulates the function of hypothalamic neurons, leading to alterations in food intake and in energy homeostasis. Here we review selected findings in the field of mitochondrial dynamics and their relevance for neurodegeneration and hypothalamic dysfunction.

  3. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Alvarez Herrero, Susana; Pinchenko, Volodymyr; Klein, Dennis;

    2011-01-01

    Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and...... conventional nerve conduction studies, behavioural studies using rotor-rod measurements, and histological measures to assess membrane dysfunction and its progression in protein zero deficient homozygous mutants as compared with age-matched wild-type controls. The involvement of Na(V)1.8 was investigated by...... pharmacologic block using the subtype-selective Na(V)1.8 blocker A-803467 and chronically in Na(V)1.8 knock-outs. We found that in the context of dysmyelination, abnormal potassium ion currents and membrane depolarization, the ectopic Na(V)1.8 channels further impair the motor axon excitability in protein zero...

  4. Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs.

    Science.gov (United States)

    Hashiguchi, Akihiro; Higuchi, Yujiro; Nomura, Miwa; Nakamura, Tomonori; Arata, Hitoshi; Yuan, Junhui; Yoshimura, Akiko; Okamoto, Yuji; Matsuura, Eiji; Takashima, Hiroshi

    2014-12-01

    To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light-chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype. PMID:25583183

  5. Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1.

    Science.gov (United States)

    Strickland, Alleene V; Schabhüttl, Maria; Offenbacher, Hans; Synofzik, Matthis; Hauser, Natalie S; Brunner-Krainz, Michaela; Gruber-Sedlmayr, Ursula; Moore, Steven A; Windhager, Reinhard; Bender, Benjamin; Harms, Matthew; Klebe, Stephan; Young, Peter; Kennerson, Marina; Garcia, Avencia Sanchez Mejias; Gonzalez, Michael A; Züchner, Stephan; Schule, Rebecca; Shy, Michael E; Auer-Grumbach, Michaela

    2015-09-01

    Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) encodes a necessary subunit of the cytoplasmic dynein complex, which traffics cargo along microtubules. Dominant DYNC1H1 mutations are implicated in neural diseases, including spinal muscular atrophy with lower extremity dominance (SMA-LED), intellectual disability with neuronal migration defects, malformations of cortical development, and Charcot-Marie-Tooth disease, type 2O. We hypothesized that additional variants could be found in these and novel motoneuron and related diseases. Therefore, we analyzed our database of 1024 whole exome sequencing samples of motoneuron and related diseases for novel single nucleotide variations. We filtered these results for significant variants, which were further screened using segregation analysis in available family members. Analysis revealed six novel, rare, and highly conserved variants. Three of these are likely pathogenic and encompass a broad phenotypic spectrum with distinct disease clusters. Our findings suggest that DYNC1H1 variants can cause not only lower, but also upper motor neuron disease. It thus adds DYNC1H1 to the growing list of spastic paraplegia related genes in microtubule-dependent motor protein pathways. PMID:26100331

  6. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

    Directory of Open Access Journals (Sweden)

    Cecilia Bucci

    2014-10-01

    Full Text Available Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC and p75NTR, a member of the tumor necrosis factor (TNF receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways.

  7. Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.

    Science.gov (United States)

    Kozol, Robert A; Abrams, Alexander J; James, David M; Buglo, Elena; Yan, Qing; Dallman, Julia E

    2016-01-01

    Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT). We also conduct a small meta-analysis of zebrafish orthologs of high confidence neurodevelopmental disorder and neurodegenerative disease genes by looking at duplication rates and relative protein sizes. In the past zebrafish genetic models of these neurodevelopmental disorders and neurodegenerative diseases have provided insight into cellular, circuit and behavioral level mechanisms contributing to these conditions. Moving forward, advances in genetic manipulation, live imaging of neuronal activity and automated high-throughput molecular screening promise to help delineate the mechanistic relationships between different types of neurological conditions and accelerate discovery of therapeutic strategies. PMID:27458342

  8. Charcot-Marine-Tooth CMT-2 Polyneuropathy Syndrome A Case Study.

    Directory of Open Access Journals (Sweden)

    Arbind Kumar Choudhary

    2015-06-01

    Full Text Available Abstract Charcot-Marie-Tooth disease CMT refers to the inherited peripheral neuropathies affect approximately one in 2500 people they are among the most common inherited neurological disorders. The majority of CMT patients have autosomal dominant inheritance although X-linked dominant and autosomal recessive forms also exist. The majority of cases are demyelinating although up to one third appear to be primary axonal or neuronal disorders. A patient of 9-year-old girl visited our hospital because of began to suffer from an insidious onset of progressive distal weakness and numbness and muscle twitching in both in her upper and lower limbs. Nerve conduction studies showed sensory nerve conduction SNCV of bilateral median and ulnar nerve was reduced in upper limb and bilateral sural nerve was reduced in lower limb While in case of motor nerve conduction MNCV bilateral median and ulnar nerve was reduced in upper limb and common peroneal nerve CPN as well as posterior tibial nerve was decreased leg. F response latencies were markedly prolonged in patient. Family history along with electrophysiological studied showed It was typical case of autosomal dominant CMT 2 axonal neuropathy. CMT is currently an untreatable disorder and at the moment the treatment of CMT is only supportive as there are no drugs available that would halt the disease symptoms. The care of a CMT patient is challenging for the health care team.

  9. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    Science.gov (United States)

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  10. Inherited peripheral neuropathies due to mitochondrial disorders.

    Science.gov (United States)

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

    Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. PMID:24768438

  11. In vivo intracellular recordings from spinal lumbar motoneurones in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurones

    DEFF Research Database (Denmark)

    Lehnhoff, Janna; Moldovan, Mihai; Hedegaard, Anne;

    2014-01-01

    Mice deficient for the peripheral myelin binding protein zero (P0-/-) show a progressive dysmyelinating neuropathy phenotypically resembling severe forms of Charcot-Marie-Tooth (CMT) disease. Traditionally, the progression of the disease was attributed to axonal loss, but the effect of chronic...... dysmyelination remains poorly understood. In this study, in vivo electrophysiological recordings were used to assess the function of both central and axonal components of spinal lumbar motoneurones in adult P0-/- mice.Three month old P0-/- mice (n=7) and wild type (WT) littermate controls (n=5) were...... anaesthetized with Hypnorm (0.315 mg/mL fentanyl-citrate + 10 mg/mL fluanisone), Midazolam (5 mg/mL), and sterile water, mixed in the ratio 1:1:2 (induction: 0.15mL/25g, maintenance: 0.05 mL/20 minutes, S.C.). Anaesthesia during surgery was assessed by the lack of reflexes to a short noxious pinch on the hind...

  12. ENU Mutagenesis Screen to Establish Motor Phenotypes in Wild-Type Mice and Modifiers of a Pre-Existing Motor Phenotype in Tau Mutant Mice

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2011-01-01

    Full Text Available Modifier screening is a powerful genetic tool. While not widely used in the vertebrate system, we applied these tools to transgenic mouse strains that recapitulate key aspects of Alzheimer’s disease (AD, such as tau-expressing mice. These are characterized by a robust pathology including both motor and memory impairment. The phenotype can be modulated by ENU mutagenesis, which results in novel mutant mouse strains and allows identifying the underlying gene/mutation. Here we discuss this strategy in detail. We firstly obtained pedigrees that modify the tau-related motor phenotype, with mapping ongoing. We further obtained transgene-independent motor pedigrees: (i hyperactive, circling ENU 37 mice with a causal mutation in the Tbx1 gene—the complete knock-out of Tbx1 models DiGeorge Syndrome; (ii ENU12/301 mice that show sudden jerky movements and tremor constantly; they have a causal mutation in the Kcnq1 gene, modelling aspects of the Romano-Ward and Jervell and Lange-Nielsen syndromes; and (iii ENU16/069 mice with tremor and hypermetric gait that have a causal mutation in the Mpz (Myelin Protein Zero gene, modelling Charcot-Marie-Tooth disease type 1 (CMT1B. Together, we provide evidence for a real potential of an ENU mutagenesis to dissect motor functions in wild-type and tau mutant mice.

  13. New mutations in CMT 1 and HNPP

    Energy Technology Data Exchange (ETDEWEB)

    Vandenberghe, A.; Boucherat, M. [Faculty of Pharmacy, Lyon (France); Bonnebouche, C. [Hopital de l`Antiquaille, Lyon (France)] [and others

    1994-09-01

    The majority of mutations in CMT 1 (Charcot-Marie-Tooth disease type 1) are due to a duplication of a 1.5 Mb fragment from chromosome 17 containing the PMP22 myelin gene. In addition, micromutations are found in the genes for PMP22 and myelin Po. We collected data from over one hundred families with a duplication in 17p11.2. In about 10% of these families, a de novo mutation was observed. All parents were clinically examined as normal and correct paternity was confirmed. Some families were informative for polymorphic probes located in the duplicated region, and we could deduce a majority of new mutations to be from paternal origin. HNPP (hereditary neuropathy with liability to pressure palsies) is believed to be the reciprocal product of an unequal crossing over underlying the CMT 1 mutation and is due to a deletion of the 1.5 Mb fragment. One new HNPP mutation was found among 7 deleted HNPP families. This mutation is of paternal origin. Clinically assigned CMT 1 patients without a duplication are screened for micromutations applying the SSCP technique. In one family, a de novo mutation was found in the gene for Po.

  14. Describing the hexapeptide identity platform between the influenza A H5N1 and Homo sapiens proteomes.

    Science.gov (United States)

    Kanduc, Darja

    2010-01-01

    We searched the primary sequence of influenza A H5N1 polyprotein for hexamer amino acid sequences shared with human proteins using the Protein International Resource database and the exact peptide matching analysis program. We find that the viral polyprotein shares numerous hexapeptides with the human proteome. The human proteins involved in the viral overlap are represented by antigens associated with basic cell functions such as proliferation, development, and differentiation. Of special importance, many human proteins that share peptide sequences with influenza A polyprotein are antigens such as reelin, neurexin I-α, myosin-IXa, Bardet-Biedl syndrome 10 protein, Williams syndrome transcription factor, disrupted in schizophrenia 1 protein, amyotrophic lateral sclerosis 2 chromosomal region candidate gene 17 protein, fragile X mental retardation 2 protein, and jouberin. That is, the viral-vs-human overlap involves human proteins that, when altered, have been reported to be potentially associated with multiple neurological disorders that can include autism, epilepsy, obesity, dystonia, ataxia-telangiectasia, amyotrophic lateral sclerosis, sensorineural deafness, sudden infant death syndrome, Charcot-Marie-Tooth disease, and myelination. The present data are discussed as a possible molecular basis for understanding influenza A viral escape from immunosurveillance and for defining anti-influenza immune-therapeutic approaches devoid of collateral adverse events. PMID:20859452

  15. Describing the hexapeptide identity platform between the influenza A H5N1 and Homo sapiens proteomes

    Directory of Open Access Journals (Sweden)

    Darja Kanduc

    2010-09-01

    Full Text Available Darja KanducDepartment of Biochemistry and Molecular Biology, University of Bari, ItalyAbstract: We searched the primary sequence of influenza A H5N1 polyprotein for hexamer amino acid sequences shared with human proteins using the Protein International Resource database and the exact peptide matching analysis program. We find that the viral polyprotein shares numerous hexapeptides with the human proteome. The human proteins involved in the viral overlap are represented by antigens associated with basic cell functions such as proliferation, development, and differentiation. Of special importance, many human proteins that share peptide sequences with influenza A polyprotein are antigens such as reelin, neurexin I-a, myosin-IXa, Bardet–Biedl syndrome 10 protein, Williams syndrome transcription factor, disrupted in schizophrenia 1 protein, amyotrophic lateral sclerosis 2 chromosomal region candidate gene 17 protein, fragile X mental retardation 2 protein, and jouberin. That is, the viral-vs-human overlap involves human proteins that, when altered, have been reported to be potentially associated with multiple neurological disorders that can include autism, epilepsy, obesity, dystonia, ataxia–telangiectasia, amyotrophic lateral sclerosis, sensorineural deafness, sudden infant death syndrome, Charcot-Marie-Tooth disease, and myelination. The present data are discussed as a possible molecular basis for understanding influenza A viral escape from immunosurveillance and for defining anti-influenza immune-therapeutic approaches devoid of collateral adverse events.Keywords: peptide sharing, neurological disorders, host-pathogen relationships, viral escape from immunosurveillance

  16. Secondary structural analysis of the carboxyl-terminal domain from different connexin isoforms.

    Science.gov (United States)

    Spagnol, Gaëlle; Al-Mugotir, Mona; Kopanic, Jennifer L; Zach, Sydney; Li, Hanjun; Trease, Andrew J; Stauch, Kelly L; Grosely, Rosslyn; Cervantes, Matthew; Sorgen, Paul L

    2016-03-01

    The connexin carboxyl-terminal (CxCT) domain plays a role in the trafficking, localization, and turnover of gap junction channels, as well as the level of gap junction intercellular communication via numerous post-translational modifications and protein-protein interactions. As a key player in the regulation of gap junctions, the CT presents itself as a target for manipulation intended to modify function. Specific to intrinsically disordered proteins, identifying residues whose secondary structure can be manipulated will be critical toward unlocking the therapeutic potential of the CxCT domain. To accomplish this goal, we used biophysical methods to characterize CxCT domains attached to their fourth transmembrane domain (TM4). Circular dichroism and nuclear magnetic resonance were complementary in demonstrating the connexin isoforms that form the greatest amount of α-helical structure in their CT domain (Cx45 > Cx43 > Cx32 > Cx50 > Cx37 ≈ Cx40 ≈ Cx26). Studies compared the influence of 2,2,2-trifluoroethanol, pH, phosphorylation, and mutations (Cx32, X-linked Charcot-Marie Tooth disease; Cx26, hearing loss) on the TM4-CxCT structure. While pH modestly influences the CT structure, a major structural change was associated with phosphomimetic substitutions. Since most connexin CT domains are phosphorylated throughout their life cycle, studies of phospho-TM4-CxCT isoforms will be critical toward understanding the role that structure plays in regulating gap junction function. PMID:26542351

  17. Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy.

    Science.gov (United States)

    Sawyer, Sarah L; Cheuk-Him Ng, Andy; Innes, A Micheil; Wagner, Justin D; Dyment, David A; Tetreault, Martine; Majewski, Jacek; Boycott, Kym M; Screaton, Robert A; Nicholson, Garth

    2015-09-15

    Multiple symmetric lipomatosis (MSL) is a mitochondrial disorder with impaired brown fat metabolism that has been associated with MERRF mutations in some, but not all, patients. We studied a sibling pair and an unrelated indiviadual who presented with MSL and neuropathy to determine the genetic etiology of this disorder in patients who did not carry the MSL-associated MERRF mutation. Whole-exome sequencing was performed on the siblings, and a rare, shared homozygous mutation in MFN2 (c.2119C>T: p.R707W) was identified. The mutation was not present in their healthy siblings. In silico programs predict it to be pathogenic, and heterozygous carriers of the MFN2 p.R707W substitution are known to have Charcot-Marie-Tooth (CMT) disease. A third, unrelated patient with multiple symmetrical lipomatosis and neuropathy also harbored the same homozygous mutation and had been previously diagnosed with CMT. Functional studies in patient fibroblasts demonstrate that the p.R707W substitution impairs homotypic (MFN2-MFN2) protein interactions required for normal activity and renders mitochondria prone to perinuclear aggregation. These findings show that homozygous mutations at p.R707W in MFN2 are a novel cause of multiple symmetrical lipomatosis. PMID:26085578

  18. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing.

    Science.gov (United States)

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-31

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386

  19. Unusual presentation of hereditary neuropathy with liability to pressure palsies

    Directory of Open Access Journals (Sweden)

    Andary Michael T

    2008-01-01

    Full Text Available Abstract Background Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal-dominant painless peripheral neuropathy characterized by episodes of repeated focal pressure neuropathies at sites of entrapment/compression, with a considerable variability in the clinical course. Electrodiagnostic and genetic testing are important in the diagnostic evaluation of these patients. Case presentation We report an unusual HNPP phenotype, five compression neuropathies in four nerves in a patient with bilateral hand numbness. A 42-year-old female, presented with acute bilateral paresthesias and weakness in her hands after starting yoga exercises requiring hyperextension of her hands at the wrists. Her presentation was complicated by: a a remote history of acute onset foot drop and subsequent improvement, b previous diagnoses of demyelinating peripheral neuropathy, possibly Charcot-Marie-Tooth disease, and c exposure to leprosy. Electrodiagnostic testing showed 5 separate compression neuropathies in 4 nerves including: severe left and right ulnar neuropathies at the wrist, left and right median neuropathies at the wrist and left ulnar neuropathy at the elbow. There was a mild generalized, primarily demyelinating, peripheral polyneuropathy. Based on the clinical suspicion and electrodiagnostic findings, consistent with profound demyelination in areas of compression, genetic analysis was done which identified a deletion of the PMP-22 gene consistent with HNPP. Conclusion HNPP can present with unusual phenotypes, such as 5 separate mononeuropathies, bilateral ulnar and median neuropathies at the wrists and ulnar neuropathy at the elbow with mild peripheral demyelinating polyneuropathy associated with the PMP-22 gene deletion.

  20. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing

    Science.gov (United States)

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-01-01

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386

  1. Effect of Electroacupuncture on the Expression of Glycyl-tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2016-01-01

    Full Text Available Glycyl-tRNA synthetase (GlyRS is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot-Marie-Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR affect energy supply and excitation-contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection-induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI, decreased peroneus longus muscle weight and muscle fiber cross-sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC-IIb. The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis.

  2. Glutamate signals through mGluR2 to control Schwann cell differentiation and proliferation.

    Science.gov (United States)

    Saitoh, Fuminori; Wakatsuki, Shuji; Tokunaga, Shinji; Fujieda, Hiroki; Araki, Toshiyuki

    2016-01-01

    Rapid saltatory nerve conduction is facilitated by myelin structure, which is produced by Schwann cells (SC) in the peripheral nervous system (PNS). Proper development and degeneration/regeneration after injury requires regulated phenotypic changes of SC. We have previously shown that glutamate can induce SC proliferation in culture. Here we show that glutamate signals through metabotropic glutamate receptor 2 (mGluR2) to induce Erk phosphorylation in SC. mGluR2-elicited Erk phosphorylation requires ErbB2/3 receptor tyrosine kinase phosphorylation to limit the signaling cascade that promotes phosphorylation of Erk, but not Akt. We found that Gβγ and Src are involved in subcellular signaling downstream of mGluR2. We also found that glutamate can transform myelinating SC to proliferating SC, while inhibition of mGluR2 signaling can inhibit demyelination of injured nerves in vivo. These data suggest pathophysiological significance of mGluR2 signaling in PNS and its possible therapeutic importance to combat demyelinating disorders including Charcot-Marie-Tooth disease. PMID:27432639

  3. Phenotype expression in women with CMT1X.

    LENUS (Irish Health Repository)

    Siskind, Carly E

    2011-06-01

    Charcot-Marie-Tooth disease type 1X (CMT1X) is the second most common inherited peripheral neuropathy. Women with CMT1X typically have a less severe phenotype than men, perhaps because of X-inactivation patterns. Our objective was to determine the phenotype of women with CMT1X and whether X-inactivation patterns in white blood cells (WBCs) differ between females with CMT1X and controls. Thirty-one women with CMT1X were evaluated using the CMT neuropathy score (CMTNS) and the CMT symptom score in cross-sectional and longitudinal analyses. Lower scores correspond to less disability. WBCs were analyzed for X-inactivation pattern by androgen receptor X-inactivation assay in 14 patients and 23 controls. The 31 women\\'s mean CMTNS was 8.35. Two-thirds of the cohort had a mild CMTNS (mean 4.85) and one-third had a moderate CMTNS (mean 14.73). Three patients had a CMTNS of 0. The pattern of X-inactivation did not differ between the affected and control groups. Women with CMT1X presented with variable impairment independent of age, type of mutation, or location of mutation. No evidence supported the presence of a gap junction beta-1 (GJB1) mutation affecting the pattern of X-inactivation in blood. Further studies are planned to determine whether X-inactivation is the mechanism for CMT1X females\\' variable phenotypes.

  4. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Wang Yi

    2011-11-01

    Full Text Available Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. Results We created transgenic mice that express the coral (Discosoma sp. red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS mice expressing human mutant superoxide dismutase-1. Conclusions These novel transgenic mice will be a useful tool for better understanding

  5. A deletion in the N-myc downstream regulated gene 1 (NDRG1 gene in Greyhounds with polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Cord Drögemüller

    Full Text Available The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D. Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60 which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

  6. 核纤层蛋白病--一个基因,多种疾病%Laminopathies -one gene, multiple diseases

    Institute of Scientific and Technical Information of China (English)

    宋书娟; 章远志; Nanbert ZHONG

    2005-01-01

    @@ 核纤层蛋白病(laminopathies)是指由LMNA基因及其编码蛋白lamin A/C异常引起的一组人类遗传病[1].根据临床特征不同,至今被认识的核纤层蛋白病已有10种,除一种由影响成熟lamin A形成的FACE-1基因突变引起外[2],其余9种均由LMNA基因突变引起,其中包括2种既可以常染色体显性又可以常染色体隐性遗传的遗传病:Emery-Dreifuss 肌营养不良(Emery-Dreifuss muscular dystrophy, EDMD,常显EDMD2,常隐EDMD3)[3,4] 和腓骨肌萎缩症2型(Charcot-Marie-Tooth2,常显AD-CMT2,常隐AR-CMT2)[5,6];6种常染色体显性遗传病:肢带型肌营养不良1B(limb girdle muscular dystrophy1B,LGMD1B)[7],扩张性心肌病伴心脏传导阻滞1A(dilated cardiomyopathy and cardiac conduction defects1A, CMD1A)[8],家族部分性脂肪营养不良(familial partial lipodystrophy, FPLD)[9],脂肪营养不良、胰岛素抵抗型糖尿病、弥漫性白黑皮病样丘疹、肝脂肪变性和心肌病综合征(lipoatrophy & insulin-resistant diabetes & disseminated leukomelanodermic papules & liver steatosis and cardiomyopathy,LDHPC)[10],Werner综合征(Werner syndrome, WRN)[11]和早老症(Hutchinson-Gilford progeria syndrome,HGPS)[12];1种常染色体隐性遗传病: Mandibuloacral dysplasia(MAD)[13].

  7. Expression of myotubularins in blood platelets: Characterization and potential diagnostic of X-linked myotubular myopathy.

    Science.gov (United States)

    Mansour, Rana; Severin, Sonia; Xuereb, Jean-Marie; Gratacap, Marie-Pierre; Laporte, Jocelyn; Buj-Bello, Ana; Tronchère, Hélène; Payrastre, Bernard

    2016-07-29

    Phosphoinositides play a key role in the spatiotemporal control of central intracellular processes and several specific kinases and phosphatases regulating the level of these lipids are implicated in human diseases. Myotubularins are a family of 3-phosphatases acting specifically on phosphatidylinositol 3-monophosphate and phosphatidylinositol 3,5 bisphosphate. Members of this family are mutated in genetic diseases including myotubularin 1 (MTM1) and myotubularin-related protein 2 (MTMR2) which mutations are responsible of X-linked centronuclear myopathy and Charcot-Marie-Tooth neuropathy, respectively. Here we show that MTM1 is expressed in blood platelets and that hundred microliters of blood is sufficient to detect the protein by western blotting. Since the most severe cases of pathogenic mutations of MTM1 lead to loss of expression of the protein, we propose that a minimal amount of blood can allow a rapid diagnostic test of X-linked myotubular myopathy, which is currently based on histopathology of muscle biopsy and molecular genetic testing. In platelets, MTM1 is a highly active 3-phosphatase mainly associated to membranes and found on the dense granules and to a lesser extent on alpha-granules. However, deletion of MTM1 in mouse had no significant effect on platelet count and on platelet secretion and aggregation induced by thrombin or collagen stimulation. Potential compensation by other members of the myotubularin family is conceivable since MTMR2 was easily detectable by western blotting and the mRNA of several members of the family increased during in vitro differentiation of human megakaryocytes and MEG-01 cells. In conclusion, we show the presence of several myotubularins in platelets and propose that minimal amounts of blood can be used to develop a rapid diagnostic test for genetic pathologies linked to loss of expression of these phosphatases. PMID:27155155

  8. Clinical use of creatine in neuromuscular and neurometabolic disorders.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2007-01-01

    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns. PMID:18652078

  9. Behavioral and molecular exploration of the AR-CMT2A mouse model Lmna (R298C/R298C).

    Science.gov (United States)

    Poitelon, Yannick; Kozlov, Serguei; Devaux, Jerôme; Vallat, Jean-Michel; Jamon, Marc; Roubertoux, Pierre; Rabarimeriarijaona, Sitraka; Baudot, Cécile; Hamadouche, Tarik; Stewart, Colin L; Levy, Nicolas; Delague, Valérie

    2012-03-01

    In 2002, we identified LMNA as the first gene responsible for an autosomal recessive axonal form of Charcot-Marie-Tooth disease, AR-CMT2A. All patients were found to be homozygous for the same mutation in the LMNA gene, p.Arg298Cys. In order to investigate the physiopathological mechanisms underlying AR-CMT2A, we have generated a knock-in mouse model for the Lmna p.Arg298Cys mutation. We have explored these mice through an exhaustive series of behavioral tests and histopathological analyses, but were not able to find any peripheral nerve phenotype, even at 18 months of age. Interestingly at the molecular level, however, we detect a downregulation of the Lmna gene in all tissues tested from the homozygous knock-in mouse Lmna (R298C/R298C) (skeletal muscle, heart, peripheral nerve, spinal cord and cerebral trunk). Importantly, we further reveal a significant upregulation of Pmp22, specifically in the sciatic nerves of Lmna (R298C/R298C) mice. These results indicate that, despite the absence of a perceptible phenotype, abnormalities exist in the peripheral nerves of Lmna (R298C/R298C) mice that are absent from other tissues. Although the mechanisms leading to deregulation of Pmp22 in Lmna (R298C/R298C) mice are still unclear, our results support a relation between Lmna and Pmp22 and constitute a first step toward understanding AR-CMT2A physiopathology. PMID:22331516

  10. Mutant glycyl-tRNA synthetase (Gars ameliorates SOD1(G93A motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice.

    Directory of Open Access Journals (Sweden)

    Gareth T Banks

    Full Text Available BACKGROUND: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs. METHODOLOGY/PRINCIPAL FINDINGS: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201. Heterozygous Gars(C201R/+ mice have locomotor and sensory deficits. In an investigation of genetic mutations that lead to death of motor and sensory neurons, we have crossed the Gars(C201R/+ mice to two other mutants: the TgSOD1(G93A model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1(Loa which has a defect in the heavy chain of the dynein complex. We found the Dync1h1(Loa/+;Gars(C201R/+ double heterozygous mice are more impaired than either parent, and this is may be an additive effect of both mutations. Surprisingly, the Gars(C201R mutation significantly delayed disease onset in the SOD1(G93A;Gars(C201R/+ double heterozygous mutant mice and increased lifespan by 29% on the genetic background investigated. CONCLUSIONS/SIGNIFICANCE: These findings raise intriguing possibilities for the study of pathogenetic mechanisms in all three mouse mutant strains.

  11. An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.

    Directory of Open Access Journals (Sweden)

    Kari J Ekenstedt

    2014-10-01

    Full Text Available An inherited polyneuropathy (PN observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006 utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC. This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

  12. Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment.

    Science.gov (United States)

    Napiontek, Marek; Pietrzak, Krzysztof

    2015-02-01

    The purpose of the paper was to present the results of surgical treatment of foot deformities in peripheral neuropathies using bone procedures: both joint preserving and with joint arthrodesis. The study included 26 patients, 14 males and 12 females (43 feet). The age of the patients at surgery ranged from 5 to 55 years (average 23 years). The follow-up ranged from 0.5 to 15 years (average 4.3 years). Seventeen patients presented Charcot-Marie-Tooth disease, three Friedreich's ataxia and six peripheral motor and sensory neuropathies of undetermined nature. Sixteen patients had bilateral procedures. Four patients had to be re-operated during the follow-up. The patients were divided into four groups depending on the age and the surgical technique applied. The groups I and II (9 children, 17 feet) included patients with growth plate still present in the foot just before surgery. In the groups III and IV (17 adults, 26 feet), bone growth was completed. The assessment of all patients based on a modified AOFAS scale ranged from 44 to 105 points (mean 83.7; SD 17.5). The assessment on the subjective scale ranged from 3 to 10 points (mean 7.4; SD 2.1). The assessment of quality of life on the WOMAC scale ranged from 0 to 41 points (mean 15.7; SD 13.2). All patients stated that they would decide to undergo the treatment again. For groups I and II, joint preserving surgeries gave better results; however, the results could not be statistically confirmed. The results for the groups III and IV were inconclusive as to which surgical techniques should be preferred, arthrodesis or joint preserving. The results show that none of the surgical techniques used for correction of foot deformities in motor-sensory polyneuropathies seems to be preferable. PMID:24968792

  13. Functional and comparative genomics analyses of pmp22 in medaka fish

    Directory of Open Access Journals (Sweden)

    Kawarabayasi Yutaka

    2009-06-01

    Full Text Available Abstract Background Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A. The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV. Several CMT1A model rodents have been established by overexpressing pmp22. Thus, it is thought that pmp22 expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between pmp22 transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for pmp22 regulation by comparative genomics analyses between jawed fishes and mammals. Results A transgenic pmp22 over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS was observed. We successfully confirmed that medaka fish pmp22 has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR. Conclusion Medaka fish undergo abnormalities in the PNS when pmp22 transcription increases. This result indicates that an adequate pmp22 transcription level is necessary for correct myelination of jawed vertebrates. Comparison of pmp22 orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of pmp22 expression.

  14. Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat.

    Science.gov (United States)

    Liška, František; Chylíková, Blanka; Janků, Michaela; Šeda, Ondřej; Vernerová, Zdeňka; Pravenec, Michal; Křen, Vladimír

    2016-09-01

    In the inbred SHR/OlaIpcv rat colony, we identified males with small testicles and inability to reproduce. By selectively breeding their parents, we revealed the infertility to segregate as an autosomal recessive Mendelian character. No other phenotype was observed in males, and females were completely normal. By linkage using a backcross with Brown Norway strain, we mapped the locus to a 1.2Mbp segment on chromosome 7, harboring 35 genes. Sequencing of candidate genes revealed a G to A substitution in a canonical 'AG' splice site of intron 37 in Sbf1 (SET binding factor 1, alias myotubularin-related protein 5). This leads to either skipping exon 38 or shifting splicing one base downstream, invariantly resulting in frameshift, premature stop codon and truncation of the protein. Western blotting using two anti-Sbf1 antibodies revealed absence of the full-length protein in the mutant testis. Testicles of the mutant males were significantly smaller compared with SHR from 4weeks, peaked at 84% wild-type weight at 6weeks and declined afterward to 28%, reflecting massive germ cell loss. Histological examination revealed lower germ cell number; latest observed germ cell stage were round spermatids, resulting in the absence of sperm in the epididymis (azoospermia). SBF1 is a member of a phosphatase family lacking the catalytical activity. It probably modulates the activity of a phosphoinositol phosphatase MTMR2. Human homozygotes or compound heterozygotes for missense SBF1 mutations exhibit Charcot-Marie-Tooth disease (manifested mainly as progressive neuropathy), while a single mouse knockout reported in the literature identified male infertility as the only phenotype manifestation. PMID:27335132

  15. Chapter 15 Juvenile amyotrophic lateral sclerosis.

    Science.gov (United States)

    Orban, Paul; Devon, Rebecca S; Hayden, Michael R; Leavitt, Blair R

    2007-01-01

    Several forms of genetically defined juvenile amy-otrophic lateral sclerosis (ALS) have now been charac-terized and discussion of these conditions will form the basis for this chapter. ALS2 is an autosomal recessive form of ALS with a juvenile onset and very slow progression that mapped to chromosome 2q33. Nine different mutations have been identified in the ALS2 gene that result in premature stop codons, suggesting a loss of function in the gene product, alsin. The alsin protein is thought to function as a guanine-nucleotide exchange factor for GTPases and may play a role in vesicle transport or membrane trafficking processes. ALS4 is an autosomal dominant form of juvenile onset ALS associated with slow progression, severe muscle weakness and pyramidal signs, in the absence of bulbar and sensory abnormalities. Mutations in the SETX gene cause ALS4, and the SETX gene product senataxin may have DNA and RNA helicase activity and play a role in the regulation of RNA and/or DNA in the cell. A third form of juvenile-onset ALS (ALS5) is associated with slowly progressing lower motor neuron signs (weak-ness and atrophy) initially of the hands and feet, with eventual bulbar involvement. Progressive upper motor neuron disease becomes more obvious with time. ALS5 has been linked to a 6 cM region of chromosome 15q15.1-q21.1, but the causative gene mutation for ALS5 has yet to be identified. The high degree of clin-ical and genetic heterogeneity in the various forms of juvenile ALS can make differential diagnosis difficult, other genetic disorders that must be considered include: spinal muscular atrophy, hereditary spastic paraplegia, SBMA, GM2 gangliosidosis and the hereditary motor neuronopathies/motor forms of Charcot-Marie-Tooth disease. Acquired disorders that must also be consid-ered include heavy metal intoxications (especially lead), multifocal motor neuropathy, paraneoplastic syndromes, vitamin deficiencies (B12) and infections (HTLV-II, HIV and poliomyelitis). PMID

  16. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of...... human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not...... stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The...

  17. Crystal structure of the extracellular domain of human myelin protein zero

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

    2012-03-27

    Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125

  18. Neurite hipertrófica intersticial: estudo de três casos

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1978-09-01

    Full Text Available São relatados 3 casos de neuropatia hipertrófica intersticial que apresentam conduções nervosas motoras bastante reduzidas; no estudo anatomopatológico foram encontradas estruturas em forma de "casca de cebola", com proliferação de tecido conjuntivo. São abordadas as teorias sobre a formação das "cascas de cebola" e a correlação com a diminuição da velocidade de condução nervosa. Os autores concluem que somente um dos casos corresponde a descrição original de Dejerine-Sottas, sendo que os outros são provavelmente doença de Charcot-Marie-Tooth.

  19. Lack of on-going adaptations in the soleus muscle activity during walking in patients affected by large-fiber neuropathy

    DEFF Research Database (Denmark)

    Nazarena, Mazzaro; Grey, Michael James; Sinkjær, Thomas;

    2005-01-01

    The aim of this study was to investigate the contribution of feedback from large-diameter sensory fibers to the adaptation of soleus muscle activity after small ankle trajectory modifications during human walking. Small-amplitude and slow-velocity ankle dorsiflexion enhancements and reductions were...... applied during the stance phase of the gait cycle to mimic the normal variability of the ankle trajectory during walking. Patients with demyelination of large sensory fibers (Charcot-Marie-Tooth type 1A and antibodies to myelin-associated glycoprotein neuropathy) and age-matched controls participated in...... this study. The patients had absent light-touch sense in the toes and feet and absent quadriceps and Achilles tendon reflexes, indicating functional loss of large sensory fibers. Moreover, their soleus stretch reflex response consisted of a single electromyographic (EMG) burst with delayed onset and...

  20. Possível parentesco entre as moléstias familiares com lesões predominantes na medula e moléstias familiares com lesões no neurônio periférico

    Directory of Open Access Journals (Sweden)

    Paulino W. Longo

    1943-06-01

    Full Text Available Os AA., depois de descreverem em linhas gerais as características da atrofia muscular progressiva e familiar tipo Charcot-Marie-Tooth, assinalam suas semelhanças com as atrofias musculares tipo Dejerine-Sottas e Werdnig-Hoffmann. Chamam atenção a seguir para a tendência, aliás já antiga de se reunir as moléstias familiares clássicas em um só grupo, pois as formas de transição entre umas e outras são bastante frequentes. A êsse respeito lembram que Austregésilo, desde 1918, defendeu essa teoria com abundância de documentação, procurando reuni-las em tôrno do que êle chama grande família hipotrófica cuja entidade central é a moléstia de Friedreich. A contribuição que trazem ao assunto é a observação de tres irmãos, membros de uma família em cujos ancestrais já havia sido assinalada paraplegia progressiva, e que apresentam o quadro neurológico típico da moléstia Charcot-Marie-Tooth, acrescido, num deles, de um síndromo piramidal bilateral (reflexos profundos exaltados, clonus da rótula e pés, sinal de Babinski e em outro, de exaltação dos reflexos patelares. Esta associação, em uma moléstia familiar degenerativa do neurônio periférico, de um quadro degenerativo cordonal, é mais um argumento favorável à unidade nosológica de todas estas moléstias familiares sistematizadas.

  1. Lung Disease

    Science.gov (United States)

    ... ePublications > Our ePublications > Lung disease fact sheet ePublications Lung disease fact sheet This information in Spanish (en ... disease? More information on lung disease What is lung disease? Lung disease refers to disorders that affect ...

  2. Glomerular Diseases

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  3. Kawasaki Disease

    Science.gov (United States)

    ... Content Article Body What is Kawasaki disease? Kawasaki disease is a serious and perplexing disease, the cause of which is ... influenza) with aspirin has been linked with a serious disease called Reye syndrome. Always consult your pediatrician before ...

  4. Ribbing disease

    International Nuclear Information System (INIS)

    Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc

  5. Alzheimer's Disease

    Science.gov (United States)

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  6. Infectious Diseases

    Science.gov (United States)

    Infectious diseases kill more people worldwide than any other single cause. Infectious diseases are caused by germs. Germs are tiny living ... to live NIH: National Institute of Allergy and Infectious Diseases

  7. Heart Disease

    Science.gov (United States)

    ... Got Homework? Here's Help White House Lunch Recipes Heart Disease KidsHealth > For Kids > Heart Disease Print A A ... chest pain, heart attacks, and strokes . What Is Heart Disease? The heart is the center of the cardiovascular ...

  8. Lyme disease

    Science.gov (United States)

    ... Causes Lyme disease is caused by bacteria called Borrelia burgdorferi ( B burgdorferi ). Blacklegged ticks and other species of ... Names Borreliosis; Bannwarth syndrome Images Lyme disease organism, Borrelia burgdorferi Tick, deer engorged on the skin Lyme disease - ...

  9. Huntington's Disease

    Science.gov (United States)

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...

  10. Krabbe disease

    Science.gov (United States)

    ... for Krabbe disease. Some people have had a bone marrow transplant in the early stages of the disease, but ... counseling is recommended for people with a family history of Krabbe disease who are considering having children. ...

  11. Stargardt Disease

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... for retinal degenerative diseases like retinitis pigmentosa (RP), Usher syndrome and macular degeneration . Back to top What ...

  12. Reportable diseases

    Science.gov (United States)

    Notifiable diseases ... Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System (NNDSS). Last updated May 4, 2015. Available at: wwwn.cdc.gov/nndss . Accessed September 9, 2015.

  13. Crohn's Disease

    Science.gov (United States)

    Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...

  14. Wilson Disease

    Science.gov (United States)

    ... Wilson disease. Health care providers do not use brain imaging tests to diagnose Wilson disease, though certain findings ... testing. [ Top ] Clinical Trials The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and other ...

  15. Farber's Disease

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Farber's Disease Information Page Synonym(s): Ceramidase Deficiency Table of Contents ( ... Trials Related NINDS Publications and Information What is Farber's Disease? Farber’s disease, also known as Farber's lipogranulomatosis, describes ...

  16. Sandhoff Disease

    Science.gov (United States)

    ... body. Sandhoff disease is a severe form of Tay-Sachs disease, the incidence of which had been particularly ... gene therapy seen in an animal model of Tay-Sachs and Sandhoff diseases for use in humans. NIH ...

  17. Legionnaires' Disease

    Science.gov (United States)

    ... lung disease Have a weak immune system Legionnaires' disease is serious and can be life-threatening. However, most people recover with antibiotic treatment. Centers for Disease Control and Prevention

  18. Ribbing disease

    Directory of Open Access Journals (Sweden)

    Mukkada Philson

    2010-01-01

    Full Text Available Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc.

  19. Celiac Disease

    OpenAIRE

    Hero Brokalaki; Nikolaos Fotos

    2008-01-01

    Celiac disease is a small intestine disease caused by the immunological response to gluten, a component of wheat, rye and barley. The worldwide prevalence of celiac disease ranges between 0.2% and 2.2 %. The clinical features of celiac disease includes diarrhea, steatorrhea, flatulence, abdominal pain and weight loss. The asymptomatic type of celiac disease is characterized by soft or normally shaped stool, weakness, lassitude and moderate weight loss. In children, celiac disease usually aris...

  20. Parkinson's disease.

    OpenAIRE

    Playfer, J R

    1997-01-01

    Parkinson's disease is a common disabling disease of old age. The diagnosis of idiopathic Parkinson's disease is based on clinical signs and has poor sensitivity, with about 25% of patients confidently diagnosed as having the disease actually having other conditions such as multi-system atrophy and other parkinsonism-plus syndromes. Benign essential tremor and arteriosclerotic pseudo-parkinsonism can easily be confused with Parkinson's disease. The cause of Parkinson's disease remains unknown...

  1. Newcastle disease

    Science.gov (United States)

    Newcastle disease (ND), referred to as Exotic Newcastle disease (END) in the U. S., is an acute viral disease of domestic poultry and many other bird species and a recognized worldwide problem. Occurrence of END is due to an infection with virulent strains of Newcastle disease virus (NDV) and is a ...

  2. Heart Diseases

    Science.gov (United States)

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the U.S. ... of disability. There are many different forms of heart disease. The most common cause of heart disease is ...

  3. Whipple's Disease

    Science.gov (United States)

    ... Disease Organizations​​ (PDF, 341 KB)​​​​​ Alternate Language URL Whipple Disease Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is Whipple disease? Whipple disease is a rare bacterial infection ...

  4. [Prion diseases].

    Science.gov (United States)

    Stoĭda, N I; Zavalishin, I A

    2012-01-01

    Prion diseases are a family of progressive neurodegenerative disorders caused by prions. There are four human prion diseases: Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, fatal insomnia and Kuru. They can arise in three different ways: acquired, familial or sporadic. We review clinical presentations, pathophysiology, morphological picture, diagnostic procedures and available treatment options of prion diseases. PMID:23235426

  5. Heart Diseases

    Science.gov (United States)

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  6. Lyme Disease

    OpenAIRE

    Weil, M L

    1989-01-01

    Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicr...

  7. Wilson Disease

    Science.gov (United States)

    Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...

  8. Chagas Disease

    Science.gov (United States)

    Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...

  9. Legionnaires' Disease

    Science.gov (United States)

    Legionnaires' disease is a type of pneumonia caused by bacteria. You usually get it by breathing in mist from ... spread from person to person. Symptoms of Legionnaires' disease include high fever, chills, a cough, and sometimes ...

  10. Parkinson's Disease

    Science.gov (United States)

    Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

  11. Raynaud's Disease

    Science.gov (United States)

    Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...

  12. Addison Disease

    Science.gov (United States)

    ... blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...

  13. Gaucher Disease

    Science.gov (United States)

    Gaucher disease is a rare, inherited disorder in which you do not have enough of an enzyme called glucocerebrosidase. ... It usually starts in childhood or adolescence. Gaucher disease has no cure. Treatment options for types 1 ...

  14. Fifth Disease

    Science.gov (United States)

    Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...

  15. Meniere's Disease

    Science.gov (United States)

    Meniere's disease is a disorder of the inner ear. It can cause severe dizziness, a roaring sound in your ... together over several days. Some people with Meniere's disease have "drop attacks" during which the dizziness is ...

  16. Valve Disease

    Science.gov (United States)

    ... Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden Cardiac Arrest Vulnerable Plaque Valve Disease | Share Related terms: heart valves, valve insufficiency, valve regurgitation, valve stenosis, valvular ...

  17. Fifth disease

    Science.gov (United States)

    Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and mouth ...

  18. Endocrine Diseases

    Science.gov (United States)

    ... Fibrosis Research Identifies Key Hurdle in Quest for Cystic Fibrosis Treatment More Research News Clinical Trials Clinical trials offer ... people and opportunities to help researchers find better treatments in the ... Fibrosis Graves' Disease Hashimoto's Disease Human Growth Hormone and ...

  19. Autoimmune Diseases

    Science.gov (United States)

    ... Some examples of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, ... Toll-Free: 877-226-4267 National Institute of Diabetes and Digestive and Kidney Diseases, NIH, HHS Phone: ...

  20. Heart Disease

    Science.gov (United States)

    ... Added Sugar Intake and Cardiovascular Diseases Mortality Among US Adults, examines the relationship between consuming too much added sugar and the risk of heart disease death. When it Comes to Blood Pressure, Make Control ...

  1. Huntington disease

    Science.gov (United States)

    Huntington chorea ... Huntington disease is caused by a genetic defect on chromosome 4. The defect causes a part of ... 10 to 28 times. But in persons with Huntington disease, it is repeated 36 to 120 times. ...

  2. Autoinflammatory Diseases

    Science.gov (United States)

    ... descriptions of some of the more common autoinflammatory diseases. The Immune System Familial Mediterranean Fever (FMF) Neonatal Onset Multisystem ... and monocytes to destroy harmful substances. In autoinflammatory diseases, this innate immune system causes inflammation for unknown reasons. It reacts, ...

  3. Legionnaire disease

    Science.gov (United States)

    ... features on this page, please enable JavaScript. Legionnaire disease is an infection of the lungs and airways. It is caused by Legionella bacteria. Causes The bacteria that cause Legionnaire disease have ...

  4. Addison disease

    Science.gov (United States)

    ... or fungal infections Hemorrhage into the adrenal glands Tumors Risk factors for the autoimmune type of Addison disease include other autoimmune diseases : Swelling (inflammation) of the thyroid gland that often results in reduced thyroid function ( chronic ...

  5. Lyme Disease

    Science.gov (United States)

    ... enabling JavaScript. Top Banner Content Area Skip Content Marketing Share this: Main Content Area Lyme Disease Lyme ... research with the major goals of developing better means of diagnosing, treating, and preventing the disease. To accomplish ...

  6. Celiac Disease

    Science.gov (United States)

    ... disease early before it causes damage to the intestine. But because it's easy to confuse the symptoms with other intestinal disorders, such as irritable bowel syndrome, inflammatory bowel disease , or lactose intolerance , teens with ...

  7. Parasitic Diseases

    Science.gov (United States)

    ... water, a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... can be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  8. Fifth Disease

    Science.gov (United States)

    ... are otherwise healthy. But for some people fifth disease cause serious health complications. People with weakened immune systems caused ... transplants, or HIV infection are at risk for serious complications from fifth disease. It can cause chronic anemia that requires medical ...

  9. Menetrier's Disease

    Science.gov (United States)

    ... with a weakened immune system, CMV can cause serious disease, such as retinitis, which can lead to blindness. ... weakened immune system in order to prevent a serious disease from developing as a result of CMV. Antiviral ...

  10. Legionnaires' Disease

    Science.gov (United States)

    ... common name for one of the several illnesses caused by Legionnaires' disease bacteria (LDB). Legionnaires' disease is an infection of the ... Legion Convention in Philadelphia. L. pneumophila had undoubtedly caused previous ... disease bacteria (LDB). L. pneumophila is a gram-negative rod ...

  11. Autoinflammatory Diseases

    International Nuclear Information System (INIS)

    We present a review article on the autoinflammatory diseases, narrating its historical origin and describing the protein and molecular structure of the Inflammasome, the current classification of the autoinflammatory diseases and a description of the immuno genetics and clinical characteristics more important of every disease.

  12. Paddlefish Diseases

    Czech Academy of Sciences Publication Activity Database

    Durborow, R.M.; Kuchta, Roman; Scholz, Tomáš

    Hoboken, New Jersey: John Wiley & Sons, Inc, 2015 - (Mims, S.; Shelton, W.), s. 227-265 ISBN 9780813810584 Institutional support: RVO:60077344 Keywords : brown blood disease * immunity * interferon regulatory factor * paddlefish diseases * Southern Regional Aquaculture Center Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine

  13. Brain Diseases

    Science.gov (United States)

    ... know what causes some brain diseases, such as Alzheimer's disease. The symptoms of brain diseases vary widely depending on the specific problem. In some cases, damage is permanent. In other cases, treatments such as surgery, medicines, or physical therapy can correct the source of the problem or ...

  14. Lyme Disease

    OpenAIRE

    Ozdemir, Davut; İnce, Nevin

    2014-01-01

    Lyme disease (LD) is caused by the spirochete, Borrelia burgdorferi sensu lato complex. Humans are infected by a tick bite to the skin. This disease is a non-contagious infectious disease. It has been known since the 19th century. LD has a worldwide distribution. It is endemic in Europe, North and South America. There are case reports since 1990 in Turkey. The clinical presentation varies depending on the stage of the disease. Lyme disease is classified into three stages: early localized dise...

  15. Glomerular disease.

    Science.gov (United States)

    Vaden, Shelly L

    2011-08-01

    Glomerular diseases are a leading cause of chronic kidney disease in dogs but seem to be less common in cats. Glomerular diseases are diverse, and a renal biopsy is needed to determine the specific glomerular disease that is present in any animal. Familial glomerulopathies occur in many breeds of dogs. However, most dogs with glomerular disease have acquired glomerular injury that is either immune-complex mediated or due to systemic factors, both of which are believed to be the result of a disease process elsewhere in the body (i.e., neoplastic, infectious, and noninfectious inflammatory disorders). A thorough clinical evaluation is indicated in all dogs suspected of having glomerular disease and should include an extensive evaluation for potential predisposing disorders. Nonspecific management of dogs with glomerular disease can be divided into 3 major categories: (1) treatment of potential predisposing disorders, (2) management of proteinuria, and (3) management of uremia and other complications of glomerular disease and chronic kidney disease. Specific management of specific glomerular diseases has not been fully studied in dogs. However, it may be reasonable to consider immunosuppressive therapy in dogs that have developed a form of glomerulonephritis secondary to a steroid-responsive disease (e.g., systemic lupus erythematosus) or have immune-mediated lesions that have been documented in renal biopsy specimens. Appropriate patient monitoring during therapy is important for maximizing patient care. The prognosis for dogs and cats with glomerular disease is variable and probably dependent on a combination of factors. The purpose of this article is to discuss the general diagnosis and management of dogs with glomerular disease. PMID:21782143

  16. Celiac Disease

    Directory of Open Access Journals (Sweden)

    Hero Brokalaki

    2008-07-01

    Full Text Available Celiac disease is a small intestine disease caused by the immunological response to gluten, a component of wheat, rye and barley. The worldwide prevalence of celiac disease ranges between 0.2% and 2.2 %. The clinical features of celiac disease includes diarrhea, steatorrhea, flatulence, abdominal pain and weight loss. The asymptomatic type of celiac disease is characterized by soft or normally shaped stool, weakness, lassitude and moderate weight loss. In children, celiac disease usually arises between the first and the third year of age, with diarrhea, flatulence and low weight. The malabsorption in small intestine causes many extaintestinal manifestations, such us anemia, bone abnormalities, hemorrhage and neuropathy. Celiac disease is diagnosed by histological examination of tissue samples taken by duodenum due gastroscopy and by the detection of certain antibodies in blood (anti-GL-IgG, anti-GL-IgA, ΕΜΑ-IgA και anti-tTg-IgA. The only therapeutic approach to celiac disease is a gluten-free diet and, if it is necessary, the administration of iron, folic acid, calcium and vitamins (K, B12. The prognosis of celiac disease is excellent, if there is an early diagnosis and the patient keeps for life a gluten free diet.

  17. Celiac disease

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2013-01-01

    Full Text Available Celiac disease is a multysystemic autoimmune disease induced by gluten in wheat, barley and rye. It is characterized by polygenic predisposition, high prevalence (1%, widely heterogeneous expression and frequent association with other autoimmune diseases, selective deficit of IgA and Down, Turner and Williams syndrome. The basis of the disease and the key finding in its diagnostics is symptomatic or asymptomatic inflammation of the small intestinal mucosa which resolves by gluten-free diet. Therefore, the basis of the treatment involves elimination diet, so that the disorder, if timely recognized and adequately treated, also characterizes excellent prognosis.

  18. [Moyamoya disease].

    Science.gov (United States)

    Esin, R G; Isayeva, Yu N; Gorobets, E A; Tokareva, N V; Esin, O R

    2016-01-01

    Moya-moya is a rare cerebrovascular disease characterized by the progressive occlusion of cerebral vessels with partial switching off the circle of Willis and arteries that feed it. The article provides a review of literature, modern diagnostic criteria and a description of a single clinical case. The onset of the disease in this patient was characterized by headache and speech disorders.An analysis of speech disorders showed that they were systemic. They were registered at all language levels (phonetic, lexical,morphological, syntactic). A long diagnostic search may be explained by clinical manifestations that are atypical for other cerebrovascular diseases and by the rarity of the disease. PMID:27386589

  19. Coeliac disease.

    Science.gov (United States)

    Green, Peter H R; Jabri, Bana

    2003-08-01

    Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten. Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners. Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas. The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium. An important component of the disease is the intraepithelial lymphocyte that might become clonally expanded in refractory sprue and enteropathy-associated T-cell lymphoma. Study of the mechanism of the immune response in coeliac disease could provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment. PMID:12907013

  20. Celiac disease

    Directory of Open Access Journals (Sweden)

    Holtmeier Wolfgang

    2006-03-01

    Full Text Available Abstract Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen; often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years.

  1. Hartnup disease

    Directory of Open Access Journals (Sweden)

    Jerajani Hemangi

    1994-01-01

    Full Text Available A rare case of Hartnup disease is presented - the patient being an 11 year old school girl suffering from a typically pellagroid rash in the absence of any other signs of malnutrition. No accompanying neurological or psychiatric features are seen, but electro-encephalography revealed abnormal baseline activity. Investigations and management are detailed and the literature on Hartnup disease reviewed.

  2. Hartnup disease

    OpenAIRE

    Jerajani Hemangi; Amladi Sangeeta; Kohli Malavika; Parekh Roopali

    1994-01-01

    A rare case of Hartnup disease is presented - the patient being an 11 year old school girl suffering from a typically pellagroid rash in the absence of any other signs of malnutrition. No accompanying neurological or psychiatric features are seen, but electro-encephalography revealed abnormal baseline activity. Investigations and management are detailed and the literature on Hartnup disease reviewed.

  3. Alexander Disease

    Science.gov (United States)

    ... Alexander disease is a progressive and often fatal disease. The destruction of white matter is accompanied by the formation of Rosenthal fibers, which are abnormal clumps of protein that accumulate in non-neuronal cells ... are sometimes found in other disorders, but not in the same amount or area ...

  4. Facioscapulohumeral disease

    NARCIS (Netherlands)

    Padberg, George Waltherus Adrianus Maria

    1982-01-01

    The purpose of this study is to discuss several aspects of facioscapulohumeral disease, also called "autosomal dominant facioscapulohumeral muscular dystrophy" or "Landouzy-Dejerine type of muscular dystrophy" or "Landouzy-Dejerine' s disease" . We consider this disorder well defined and recognizabl

  5. Tickborne Diseases

    Science.gov (United States)

    ... eye rash similar to that found in Lyme disease, which is caused by bacteria transmitted by the deer tick. Although researchers know that the lone star tick transmits the infectious agent that causes STARI, they ... both bacterial diseases. Babesiosis is caused by parasites carried by deer ...

  6. Whipple's disease

    Science.gov (United States)

    ... include: Complete blood count ( CBC ) Polymerase chain reaction (PCR) test to check for the bacteria that cause the disease Small bowel biopsy Upper GI endoscopy (viewing the intestines with a flexible, lighted tube in a process called enteroscopy ) This disease may ...

  7. Lyme Disease

    Science.gov (United States)

    ... simply be displayed as a subtle area of pink or red skin rather than the classic bull's-eye rash. Overview Lyme disease is the result of infection with the bacteria Borrelia burgdorferi. The disease is transmitted by infected ticks that also feed on mice and deer. The tick can be found attached ...

  8. Barlow's Disease

    OpenAIRE

    Sozen, Yunus V.; Tozun, Remzi; Berkman, Mahmut; Akalin, Yilmaz; Kara, Ayhan Nedim

    2004-01-01

    Scurvy that is so rare nowadays is clinically and radiologically very well defined. Two cases brought to our clinic in 1979 and 1980 are presented because ths disease process was so far advanced and because the clinical ond especsally radiological manifesations of the disease were so typical. The radiological and clinical characteristics of scurvy are elucidated because of these two cases.

  9. Parasitic diseases

    International Nuclear Information System (INIS)

    Foundations of roentgenological semiotics of parasitic diseases of lungs, w hich are of the greatest practical value, are presented. Roentgenological pictu res of the following parasitic diseases: hydatid and alveolar echinococcosis, pa ragonimiasis, toxoplasmosis, ascariasis, amebiasis, bilharziasis (Schistosomias is) of lungs, are considered

  10. Whipple's Disease

    Science.gov (United States)

    ... she sends a report to the gastroenterologist for review. Read more in Upper GI Endoscopy at www.digestive.niddk.nih.gov. How is Whipple disease treated? The health care provider prescribes antibiotics to destroy the T. whipplei bacteria and treat Whipple disease. Health care providers choose ...

  11. Pneumococcal Disease

    Science.gov (United States)

    ... 000 adults age 65 years and older. Pneumococcal disease can cause serious illness and lifelong complications. Pneumococcal meningitis can cause hearing loss, seizures, blindness, and paralysis. Serious heart problems are ... its worst forms, pneumococcal disease kills one in every four to five people ...

  12. Celiac Disease

    Directory of Open Access Journals (Sweden)

    Manoochehr Karjoo

    2014-08-01

    Full Text Available Celiac disease also known as gluten-sensitive enteropathy is characterized by intestinal mucosal damage and malabsorption from dietary intake of wheat, rye or barley. Symptoms may appear with introduction of cereal in the first 3 years of life. A second peak in symptoms occurs in adults during the third or forth decade and even as late as eight decade of life. The prevalence of this disease is approximately 1 in 250 adults. The disease is more prevalent in Ireland as high as 1 in 120 adults. The disorder occurs in Arab, Hispanics, Israeli Jews, Iranian and European but is rare in Chinese and African American. To have celiac disease the patient should have the celiac disease genetic markers as HLA DQ 2 and HLA DQ 8. Patient with celiac disease may have 95 per cent for DQ 2 and the rest is by DQ 8. Someone may have the genetic marker and never develops the disease. In general 50 percent with markers may develop celiac disease. To develop the disease the gene needs to become activated. This may happen with a viral or bacterial infection, a surgery, delivery, accident, or psychological stress. After activation of gene cause the tight junction to opens with the release of Zonulin This results in passage of gluten through the tight junction and formation of multiple antibodies and autoimmune disease. This also allows entrance of other proteins and development of multiple food allergies. As a result is shortening, flattening of intestinal villi resulting in food, vitamins and minerals malabsorption.

  13. Wilson's Disease

    Directory of Open Access Journals (Sweden)

    MH Amirian

    1986-07-01

    Full Text Available The reported case is a 9-year old female who was presented with following clinical signs and symptoms: Excessive salivation, difficulty in speaking and writing, deteriorating school performance, spasticity, dysarthria, dysphagia, tremor of the wrists and shoulders. The initial impression was Wilson's disease. Increased copper in the urine after 24 hour treatment with D-penicillamine, low serum copper level and low ceruloplasmin and presence of kayser-fleischer rings in ophthalmologic slit lamp examination confirmed the diagnosis of Wilson's disease and treatment with D-penicillamine was started. It is important to keep Wilson's disease in mind in evaluating patients with presentation similar to that of this patient. Wilson's disease is a recessively inherited defect of copper metabolism. In 70-805 of cases, the presenting clinical manifestations are hepatic or neurological. kayser-fleischer ring is present in 75% of children who present with hepatic symptoms and in all children with neurological changes. The histologic appearance of liver biopsy in Wilson's disease is not pathognomonic. The early diagnosis and treatment of Wilson's disease is extremely important, as effective therapy is available. D-penicillamine is the most effective drug in treating Wilson's disease.

  14. Crohn's disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2012-02-03

    Crohn\\'s disease is a disorder mediated by T lymphocytes which arises in genetically susceptible individuals as a result of a breakdown in the regulatory constraints on mucosal immune responses to enteric bacteria. Regulation of immune reactivity to enteric antigens has improved understanding of the pathophysiological mechanisms of Crohn\\'s disease, and has expanded therapeutic options for patients with this disorder. Disease heterogeneity is probable, with various underlying defects associated with a similar pathophysiological outcome. Although most conventional drug treatments are directed at modification of host response, therapeutic manipulation of the enteric flora is becoming a realistic option.

  15. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy

    Directory of Open Access Journals (Sweden)

    Vivien Parker

    2016-01-01

    Full Text Available Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n=42 and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP (n=20, acquired inflammatory demyelinating neuropathy (AIDP (n=13, Charcot Marie Tooth (CMT type 1 or 4C (n=15, carpal tunnel syndrome (CTS (n=11, and amyotrophic lateral sclerosis (ALS (n=18. Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA and CIDP (median nerve: 38.9 mA, whereas values similar to normal controls (median nerve: 25.3 mA were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier.

  16. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy.

    Science.gov (United States)

    Parker, Vivien; Warman Chardon, Jodi; Mills, Julie; Goldsmith, Claire; Bourque, Pierre R

    2016-01-01

    Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n = 42) and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP) (n = 20), acquired inflammatory demyelinating neuropathy (AIDP) (n = 13), Charcot Marie Tooth (CMT) type 1 or 4C (n = 15), carpal tunnel syndrome (CTS) (n = 11), and amyotrophic lateral sclerosis (ALS) (n = 18). Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA) and CIDP (median nerve: 38.9 mA), whereas values similar to normal controls (median nerve: 25.3 mA) were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier. PMID:27413732

  17. Are electrophysiological criteria useful in distinguishing childhood demyelinating neuropathies?

    Science.gov (United States)

    Potulska-Chromik, Anna; Ryniewicz, Barbara; Aragon-Gawinska, Karolina; Kabzinska, Dagmara; Seroka, Andrzej; Lipowska, Marta; Kaminska, Anna M; Kostera-Pruszczyk, Anna

    2016-03-01

    Childhood chronic inflammatory demyelinating polyneuropathy (CIDP) needs to be differentiated from hereditary neuropathy. We aimed to validate existing CIDP nerve conduction study (NCS) criteria in a group of children with demyelinating neuropathies of chronic or subacute onset. Retrospective analysis of clinical and NCS results in 18 children with CIDP, 7 with hereditary neuropathy with pressure palsy (HNPP), and 24 with Charcot-Marie-Tooth 1a (CMT1a). AAN and EFNS electrodiagnostic CIDP criteria were fulfilled in 17 of 18 CIDP, 3 of 7 HNPP, and 23 of 24 CMT1a patients. A distal compound muscle action potential (dCMAP) of >9 ms was observed in 14 of 18 CIDP patients but not in any patients with HNPP. Abnormal median/normal sural SNAP (AMNS) and a 10 m/s difference between conduction velocities (CV) of two corresponding nerves were not observed in any CMT1a patients. NCS in CMT1a, HNPP, and CIDP reflect demyelination. dCMAP duration, sensory AMNS, and a 10 m/s CV difference parameter are most useful in the differential diagnosis of pediatric CIDP. PMID:26663344

  18. Chromosomal mapping of the human M6 genes

    Energy Technology Data Exchange (ETDEWEB)

    Olinsky, S.; Loop, B.T.; DeKosky, A. [Univ. of Pittsburgh, PA (United States)] [and others

    1996-05-01

    M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis. We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2 A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders. 8 refs., 3 figs.

  19. Congenital vertical talus in four generations of the same family

    International Nuclear Information System (INIS)

    This paper presents four generations of a family with radiographically demonstrated congenital vertical talus (CVT) in whom a HOXD10 gene mutation was identified. Some members of the family with this mutation exhibited cavo-varus foot deformity consistent with a Charcot-Marie-Tooth (CMT)-like disorder. Physical examination was performed on nearly all of the affected and unaffected family members. DNA was extracted from blood obtained from 14 subjects who showed radiographic and clinical features of CVT (two of whom also had CMT), from two subjects with features of CMT but not CVT, and from 20 related family members who were clinically normal. Radiographs show the appearance of uncorrected CVT in infancy, in childhood, and in adulthood. DNA analysis revealed a mutation in a HOXD10gene located on chromosome 2 in all of the affected but none of the unaffected family members. There is an autosomal-dominant-inherited mutation with complete penetrance which is found in all members of a pedigree with CVT, some of whom exhibit a CMT-like foot disorder. Radiologic findings vary depending on the severity of involvement, treatment provided and age of the patient. (orig.)

  20. Convergence and divergence of tumor-suppressor and proto-oncogenes in chimpanzee from human chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Verma, R.S.; Ramesh, K.H. [Long Island College Hospital, Brooklyn, NY (United States)

    1994-09-01

    Due to the emergence of molecular technology, the phylogenetic evolution of the human genome via apes has become a saltatory even. In the present investigation, cosmid probes for P53, Charcot-Marie-Tooth [CMTIA], HER-2/NEU and myeloperoxidase [MPO] were used. Probes mapping to these genetic loci are well-defined on human chromosome 17 [HSA 17]. We localized these genes on chimpanzee [Pan troglodyte] chromosomes by FISH technique employing two different cell lines. Our results indicate that chimpanzee chromosome 19 [PTR 19] differs from HSA 17 by a pericentric inversion. The P53 gene assigned to HSA 17p13.1 is localized on PTR 19p15 and the MPO sequence of HSA 17q21.3-23 hybridized to PTR 19q23. Perplexing enough, HER-2/NEU assigned to HSA 17q11.2 localized to PTR 19p12. Obviously, there is convergence of P53 and MPO regions and distinctive divergence of HER-2/NEU and CMT1A regions of human and chimpanzee. This investigation has demonstrated the pronounced genetic shuffling which occurred during the origin of HSA 17. Molecular markers should serve as evolutionary punctuations in defining the precise sequence of genetic events that led to the evolution of other chromosomes whose genomic synteny, although similar, have surprisingly evolved through different mechanisms.

  1. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy

    Science.gov (United States)

    Parker, Vivien; Warman Chardon, Jodi; Mills, Julie; Goldsmith, Claire; Bourque, Pierre R.

    2016-01-01

    Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n = 42) and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP) (n = 20), acquired inflammatory demyelinating neuropathy (AIDP) (n = 13), Charcot Marie Tooth (CMT) type 1 or 4C (n = 15), carpal tunnel syndrome (CTS) (n = 11), and amyotrophic lateral sclerosis (ALS) (n = 18). Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA) and CIDP (median nerve: 38.9 mA), whereas values similar to normal controls (median nerve: 25.3 mA) were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier.

  2. Mitochondrial Diseases

    Science.gov (United States)

    ... in your body tissues. If you have a metabolic disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are small structures that produce energy in ...

  3. Chagas disease

    Science.gov (United States)

    Insect control with insecticides and houses that are less likely to have high insect populations will help control the spread of the disease. Blood banks in Central and South America screen donors for ...

  4. Pompe Disease

    Science.gov (United States)

    ... weakness progressing to respiratory weakness and death from respiratory failure after a course lasting several years. The heart ... the age of one year from either cardiorespiratory failure or respiratory infection. For individuals with late onset Pompe disease, ...

  5. Alzheimer disease

    Science.gov (United States)

    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more likely ...

  6. Menetrier's Disease

    Science.gov (United States)

    ... campuses in Maryland and Arizona Research Resources Protocols, repositories, mouse models, plasmids, and more Technology Advancement & Transfer ... through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, ...

  7. Gaucher disease

    Science.gov (United States)

    Enzyme replacement therapy is available. A bone marrow transplant may be needed in severe cases. ... is recommended for prospective parents with a family history of Gaucher disease. Testing can determine if parents ...

  8. Leishmaniasis Disease

    Science.gov (United States)

    ... please visit this page: About CDC.gov . Parasites - Leishmaniasis Parasites Home Share Compartir Disease Ulcerative skin lesion, ... border, on a Guatemalan patient who has cutaneous leishmaniasis. (Credit: B. Arana, MERTU, Guatemala) Marked splenomegaly (enlargement/ ...

  9. Legionnaires disease

    Energy Technology Data Exchange (ETDEWEB)

    McHale, P.A.

    1988-01-01

    Describes the history of legionnaires disease, its formation and occurrence, air conditioning systems and cooling towers where legionella has been shown to exist, and precautions in the mining environment. 4 figs.

  10. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  11. Sever's Disease

    Science.gov (United States)

    ... results from physical activities and sports that involve running and jumping, especially those that take place on hard surfaces, such as track, basketball, soccer, and gymnastics. Sever's disease also can result from ...

  12. Graves' Disease

    Science.gov (United States)

    ... thyroid disease may be sensitive to harmful side effects from iodine. Taking iodine drops or eating foods containing large amounts of iodine—such as seaweed, dulse, or kelp—may cause or worsen hyperthyroidism. ...

  13. Parkinson's Disease

    Science.gov (United States)

    ... about 5 to 10 percent of people with Parkinson's have "early-onset" disease which begins before the age of 50. Early-onset forms of Parkinson's are often inherited, though not always, and some ...

  14. Pick disease

    Science.gov (United States)

    ... legal advice early in the course of the disorder. Advance care directive , power of attorney, and other legal actions can make it easier to make decisions regarding the care of the person with Pick disease.

  15. Hashimoto's Disease

    Science.gov (United States)

    ... a disease that keeps your body from absorbing vitamin B12 and making enough healthy red blood cells Lupus — ... or more tests. Sometimes, routine screening of thyroid function reveals a mildly underactive thyroid in a person ...

  16. Alzheimer disease

    Science.gov (United States)

    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more ...

  17. Crohn's Disease

    Science.gov (United States)

    ... most cases, people only take this medication for short periods of time since it can increase the chance of developing megacolon. Bowel Rest Sometimes Crohn's disease symptoms are severe and a person may need to ...

  18. Behcet's Disease

    Science.gov (United States)

    ... 25 years and access publications (since 1985) and patents resulting from NIH funding. PubMed is a free ... http://www.nidcr.nih.gov National Institute of Diabetes and Digestive and Kidney Diseases Website: http://www. ...

  19. Extrapyramidal disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008119 Therapeutic effect of neuropeptide PACAP27 on Parkinson′s disease in mice. WANG Gang(王刚), et al.Dept Neurol & Neurol Instit, Ruijin Hosp, Shanghai Jiaotong Univ, Med Sch, Shanghai 200025. Chin J Neurol 2007;40(12):837-841. Objective To investigate the effects of different doses of pituitary adenylate cyclase-activating polypeptide (PACAP) on the functional and morphological outcome in a mice model of Parkinson′s disease (PD) re

  20. Celiac disease

    OpenAIRE

    Holtmeier, Wolfgang; Caspary, Wolfgang F

    2006-01-01

    Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for cli...

  1. Celiac disease

    OpenAIRE

    Holtmeier Wolfgang; Caspary Wolfgang F

    2006-01-01

    Abstract Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalenc...

  2. Extrapyramidal disease

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010380 Evaluation non-motor symptoms in Parkinson’s disease and its influence on ability of daily living. WANG Rongfei(王荣飞),et al. Dept Neurol,1st Hosp,Guangzhou Med Coll,Guangzhou 510000. Chin J Neurol 2010;43(4):273-276. Objective To evaluate the non-motor symptoms (NMS) in Parkinson’s disease (PD),and its influence on ability of daily living (ADL) in PD

  3. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  4. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... Coronary heart disease is the leading cause of death in the United States for men and women. Coronary heart disease ...

  5. Learning about Crohn's Disease

    Science.gov (United States)

    ... genetic terms used on this page. Learning About Crohn's Disease What is Crohn's disease? What are the symptoms ... disease Additional Resources for Crohn's Disease What is Crohn's disease? Crohn's disease, an idiopathic (of unknown cause), chronic ...

  6. Infection and Cardiovascular Disease

    Science.gov (United States)

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  7. Peripheral artery disease - legs

    Science.gov (United States)

    ... if they have a history of: Abnormal cholesterol Diabetes Heart disease (coronary artery disease) High blood pressure ( hypertension ) Kidney disease involving hemodialysis Smoking Stroke ( cerebrovascular disease )

  8. Celiac disease

    DEFF Research Database (Denmark)

    Hvas, Christian Lodberg; Jensen, Michael Dam; Reimer, Maria Christina;

    2015-01-01

    This national clinical guideline approved by the Danish Society for Gastroenterology and Hepatology describes the diagnosis and treatment of celiac disease (CD) in adults. CD is a chronic immunemediated enteropathy of the small intestine triggered by the ingestion of gluten-containing proteins......, which are found in wheat, rye, and barley. The disease prevalence is 0.5-1.0%, but CD remains under-diagnosed. The diagnosis relies on the demonstration of lymphocyte infiltration, crypt hyperplasia, and villous atrophy in duodenal biopsies. Serology, malabsorption, biochemical markers, and...... small intestinal mucosa and absorption. Adherence to a GFD usually requires dietary advice from a clinical dietician. The monitoring of antibody levels and malabsorption markers is crucial during follow-up and allows for early treatment of disease complications. Important complications include...

  9. Myocardial disease

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930497 Ectopic expression and the significanceof HLA—class II antigens in the myocardium ofpatients with dilated cardiomyopathy.LI Yunyou(李运友),et al.lst Affili Hosp,Nanjing MedCoil,Nanjing,210029.Chin J Cardiol 1993;21(1):15—16.Expression of HLA—class II antigens(DQ,DP)in the myocardium of patients with differentheart diseases and normal controls was studiedwith indirect immunofluorescence(IIF).Thepositive rates in different groups were observedas follows:dilated cardiomyopathy(DCM,12/13,+++),rheumatic heart disease(2/4,++),congenital heart diseases(1/14,+),left a-trial myxoma(0/1)and normal controls(1/8,

  10. Hansen's disease: a vanishing disease?

    Directory of Open Access Journals (Sweden)

    Sinésio Talhari

    2012-12-01

    Full Text Available The introduction, implementation, successes and failures of multidrug therapy (MDT in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.

  11. Meniere's Disease

    Science.gov (United States)

    ... feel better when they awaken. How can I reduce the frequency of Ménière’s disease episodes? Avoid stress and excess salt ingestion, caffeine, smoking, and alcohol. Get regular sleep and eat properly. Remain physically active, but avoid ...

  12. Parkinson's Disease

    Science.gov (United States)

    ... second most common disorder of this type after Alzheimer's disease. It progresses slowly as small clusters of ... vitamin D deficiency in the development of Parkinson's. Vitamin D, which can enter ... K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, ...

  13. Huntington's disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia;

    2011-01-01

    In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...

  14. Huntington's Disease

    Science.gov (United States)

    ... to probe the cause and progression of such circuit defects in HD. Scientists are also using stem cells to study disease mechanisms and test potential therapeutic drugs. The NINDS-funded PREDICT-HD study seeks to identify biomarkers (biological changes that can be used to predict, diagnose, ...

  15. INFECTIOUS DISEASE

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    2.1 Viral disease2004002 M gene sequence analyses on Guangdong SARS CoV isolates. ZHOU Huiqiong (周惠琼), et al. Dis Contr & Prev Center, Guangdong Prov, Guangzhou 510300. Chin J Microbiol Immunol 2003; 23 (12) : 923 -925.Objective:To analyze the variation of M gene by sequenc-

  16. Extraphyramidal disease

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009250 Effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with parkinson’s disease. WANG Xuelian(王学廉),et al.Dept Neurosurg,Tangdu Hosp,4th Milit Med Univ,Xi’an,710038.Chin J Nerv Ment Dis,2009;35(2):88-92.

  17. Neurologic Diseases

    Science.gov (United States)

    The brain, spinal cord, and nerves make up the nervous system. Together they control all the workings of the body. When something goes wrong ... develops, such as spina bifida Degenerative diseases, where nerve cells are ... to the spinal cord and brain Seizure disorders, such as epilepsy ...

  18. Prionic diseases

    Directory of Open Access Journals (Sweden)

    Abelardo Q-C Araujo

    2013-09-01

    Full Text Available Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing protein but apparently lacking nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear. Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD and its variants, Gerstmann-Sträussler-Scheinker (GSS syndrome and fatal familial insomnia (FFI] result from accumulation of abnormal isoforms of the prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal prion protein in humans (PRNP - located on the short arm of chromosome 20 – and forms of prion disease with a familial predisposition (familial CJD, GSS, FFI. Clinically a prionopathy should be suspected in any case of a fast progressing dementia with ataxia, myoclonus, or in individuals with pathological insomnia associated with dysautonomia. Magnetic resonance imaging, identification of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases.

  19. Wilson Disease

    Science.gov (United States)

    ... salts such as zinc acetate (Galzin), blocks the digestive tract’s absorption of copper from food. Although most people ... Health of the U.S. Department of Health and Human Services. Established in 1980, the ... digestive diseases to people with digestive disorders and to ...

  20. Infectious Disease

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010400 The genetic characterization of VP1 region of Coxsackie virus A10 isolated from hand, foot and mouth disease cases in Shandong Province of China.YANG He(杨赫), et al.Instit Epidemiol & Health Statistic, Sch Public Health, Shandong Univ, Jinan 250012.Chin J Infect Dis

  1. Parasitic Diseases

    Science.gov (United States)

    ... to worms that can be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies can lead to Giardia infections. Cats can transmit toxoplasmosis, which is dangerous for pregnant women. Others, like malaria, are common in other parts ...

  2. Parkinson's Disease

    Science.gov (United States)

    ... nih.gov/research/parkinsonsweb/index.htm NIH Patient Recruitment for Parkinson's Disease Clinical Trials At NIH Clinical ... 800-655-2273 Fax: 408-734-8522 Parkinson's Resource Organization ... Health and Human Services, Education, May 22, 2002. September 1999 Parkinson's ...

  3. Gum Disease

    Science.gov (United States)

    ... embarrassing (like bad breath) to the serious — like pain and tooth loss (which is both embarrassing and serious!). What ... also feed the acids that eat into your tooth enamel. If you have braces, ... certain medicines increase the risk of gum disease. Running yourself ...

  4. Celiac disease.

    Science.gov (United States)

    Rivera, E; Assiri, A; Guandalini, S

    2013-10-01

    Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals, this enteropathy may appear at any age, and is characterized by a wide variety of clinical signs and symptoms. Among them, gastrointestinal presentations include chronic diarrhea, abdominal pain, weight loss or failure to thrive in children; but extra-intestinal manifestations are also common, and actually appear to be on the rise. They include a large variety of ailments, such as dermatitis Herpetiformis, anemia, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminases, and even female infertility. For the clinician interested in oral diseases, celiac disease can lead to delayed tooth eruption, dental enamel hypoplasia, recurrent oral aphthae. Diagnosing celiac disease requires therefore a high degree of suspicion followed by a very sensitive screening test: serum levels of the autoantibody anti-tissue transglutaminase. A positive subject will then be confirmed by an intestinal biopsy, and will then be put on a strict gluten-free diet, that in most cases will bring a marked improvement of symptoms. Newer forms of treatment which in the future will probably be available to the non-responsive patients are currently being actively pursued. PMID:23496382

  5. Celiac disease

    DEFF Research Database (Denmark)

    Hvas, Christian Lodberg; Jensen, Michael Dam; Reimer, Maria Christina;

    2015-01-01

    small intestinal mucosa and absorption. Adherence to a GFD usually requires dietary advice from a clinical dietician. The monitoring of antibody levels and malabsorption markers is crucial during follow-up and allows for early treatment of disease complications. Important complications include...

  6. Lung Diseases

    Science.gov (United States)

    When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...

  7. INFECTIOUS DISEASE

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    2.1 Viral disease2003263 Isolation, identification and sequence analyses of dengue virus type 2 strain GD19/2001. REN Rui-wen(任瑞文), et al. Milit Med Instit Guangzhou Milit District, Guangzhou 510507. Chin J Epidemiol 2003; 24 (4):288-290. Objective:To identify the virus isolated from patients

  8. Parkinson's disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Aziz, Tipu Z

    2015-01-01

    -derived therapy in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from...

  9. Leigh's Disease

    Science.gov (United States)

    ... impairment of respiratory and kidney function. In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and ...

  10. Celiac Disease

    Science.gov (United States)

    ... by finding certified gluten-free foods. For instance, gluten-free oats are now available for people with celiac disease. The best approach is to read labels , but here are a few foods to steer clear of until you ... packaged rice mixes lunchmeats sausages instant cocoa ...

  11. Celiac disease

    Institute of Scientific and Technical Information of China (English)

    Luis Rodrigo

    2006-01-01

    Celiac disease (CD) is a common autoimmune disorder,induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief,this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-Ⅱ antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2(tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the "gold standard" for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis,several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin,various types of cancer and other autoimmune disorders.Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals,although its effect on some associated extraintestinal manifestations remains to be established.

  12. Bacterial disease

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930445 A report on investigation of an outbreakof legionnaires’disease in a hotel in Beijing.DENG Changying(邓长英),et al.Beijing ArmedForce General Hosp,Beijing,100027.Chin J Epi-demiol 1993;14(2):78—79.During the period from February to March,1992,an outbreak of upper respiratory infection(influenza—like syndrome)took place in a hotelin Beijing.An epidemiological investigation andbacteriological examination were carried out inthis hotel.The results showed that it was anoutbreak of Legionnaires’disease caused by Le-gionella pneumophila serogroup 10(Lpl0).Theincidence was 13.51%(5/37).This is the firstreport on Lp10 infection in China.

  13. Peyronie disease

    International Nuclear Information System (INIS)

    Peyronie disease, or Induratio Penis Plastica, is characterized by the presence of one or more fibrous plaques at the albuginea penis, on the cavernous bodies or on the intercavernous septum. First of all, Induratio Penis Plastica ethiology is described, and its clincs and therapy. Past imaging methods are then considered (i.e. conventional radiology, cavernosography, CT and US). The authors report on their 4-year (1983-1987) experience with US in 62 males. Various different probes were employed, especially small-part 7.5 MHz probes. The results are similar to those reported in international literature. The use of high frequency probes allow the evaluation of local hypoechoic lesions even in the early phase of the disease, thus helping make therapy more effective

  14. Thyroid disease

    International Nuclear Information System (INIS)

    Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications

  15. Morgellons disease?

    Science.gov (United States)

    Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John

    2008-01-01

    Morgellons disease, a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, was first described many centuries ago, but has recently been given much attention on the internet and in the mass media. The present authors present a history of Morgellons disease, in addition to which they discuss the potential benefit of using this diagnostic term as a means of building trust and rapport with patients to maximize treatment benefit. The present authors also suggest "meeting the patient halfway" and creating a therapeutic alliance when providing dermatologic treatment by taking their cutaneous symptoms seriously enough to provide both topical ointments as well as antipsychotic medications, which can be therapeutic in these patients. PMID:18318880

  16. "Chronic Lyme Disease"

    Science.gov (United States)

    ... Content Marketing Share this: Main Content Area "Chronic Lyme Disease" What is "chronic Lyme disease?" Lyme disease is an infection caused by ... J Med 357:1422-30, 2008). How is Lyme disease treated? For early Lyme disease, a short ...

  17. Sickle Cell Disease (SCD)

    Science.gov (United States)

    ... disease (SCD) Email this page Print this page Sickle cell disease (SCD) Sickle cell disease (SCD) is a disease of the hemoglobin. ... and form a sickle or a cresent. Tweet Sickle cell disease (SCD) Symptoms of SCD How transplant can ...

  18. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... Coronary heart disease is the leading cause of death in the United States for men and women. Coronary heart ...

  19. Fungal disease

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930031 Experimental studies on lung lesionsof rabbits caused by streptomyces thermohy-groscopicus.LIU Fang(刘仿),et al.Dept Mi-crobiol,Hubei Med Coll,Xianning Branch,437100.Chin J Tuberc & Respir Dis 1992;15(4):207—208.Imitating the natural way of infection ofFarmer’s lung disease,we succeeded in inducingChina Medical Abstracts(Internal Medicine)

  20. INFECTIOUS DISEASE

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    4.1 Viral disease2003021 Analysis on the epidemiologic features of Dengue fever in Guangdong province, 1990 - 2000. LUO Huiming(罗会明), et al. Dis Contr & Prev Center Guangdong Prov, Guangzhou 510300. Chin J Epi-demiol 2002;23(6):427-430.Objective: To determine the epidemiological characteristics and risk factors of Dengue fever in Guangdong province in 1990 - 2000, and to develop the strategy for

  1. Parkinson's disease.

    OpenAIRE

    Wolters, E C; Calne, D. B.

    1989-01-01

    In Parkinson's disease there is degeneration of neurons in the substantia nigra, with consequent depletion of the neurotransmitter dopamine. The triad of tremor, rigidity and bradykinesia is the clinical hallmark. Drugs currently used for palliative therapy fall into three categories: anticholinergic agents, dopamine precursors (levodopa combined with extracerebral decarboxylase inhibitors) and artificial dopamine agonists. It has been argued, on theoretical grounds, that some drugs slow the ...

  2. Infectious diseases

    International Nuclear Information System (INIS)

    Central nervous system infections represents a group of life-threatening diseases that present a formidable challenge to physicians. Despite the development of effective antimicrobial agents and modern surgical techniques, significant mortality and morbidity with CNS infections persist. Since the introduction of computed tomography, there is evidence of a marked decrease in mortality among patients with brain abscesses, although the morbidity has not changed significantly. CT correlation with pathology of the various CNS infections may aid in earlier diagnosis and bring about further disease in morbidity and mortality. Infections reach the brain or meninges mainly by two routes: (1) hematogenous dissemination from a distant infective focus to the meninges, corticomedullary junction, and choroid plexus; (2) direct extension by bony erosion for an adjacent focus of suppuration (otitis, mastoidits, sinusitis), by transmission along anaostomotic veins from the face, scalp, and orbits, and by transmission along cranial nerves following neurosurgery or traumatic craniocerebral wounds. Certain external factors serve to enhance the risk of intracranial infections, such as radiation; immunosuppressive or steroid therapy; cyanotic congenital heart disease; systemic illness such as diabetes mellitus, alcoholism, or cirrhosis; leukemia, lymphoma, or agammaglobulinemia; severe body stress; midline bony fusion defects; surgical or traumatic craniocerebral injury; and pulmonary or other systemic infections

  3. Huntington's disease

    OpenAIRE

    Bernard, Branka

    2009-01-01

    Die Huntington''sche Krankheit (Huntington''s disease, HD) ist eine tödliche neurodegenerative Erkrankung mit einem extensiven Verlust von Neuronen im Striatum. Die Ursache für HD ist eine genetische Mutation, bei der eine CAG-Wiederholungssequenz verlängert wird. Im resultierenden Protein, das Huntingtin (htt) genannt wurde, diese Mutation führt zur Missfaltung und Aggregation von htt. Ich habe untersucht ob die Bildung von htt-Aggregaten die Transkription von Genen dass sie von HD-asso...

  4. Infectious Disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    2.1 Viral disease 2006009 Correlation analysis of type A influenza virus genetic variation characteristic with survival selective pressure ZHOU xiao -ming(周晓明 ) ,et al. Sch Pub Health,Fudan Univ. Shanghai 200032. China J Infect Dis 2005;23(4) :221 -224 Objective:To study the relationship betweer. type A influenza virus genetic variation with survival selective pressure to find possible vaccine conserved antigen target. Methods:Seven strains of same HA (Hemagglutinin) serotype, regional and isolation time closely related type A influenza virus were selected with full HA gene coding sequence , Blast2 program was used to calculate the param-

  5. [Renal disease].

    Science.gov (United States)

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  6. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  7. Women's Heart Disease: Heart Disease Risk Factors

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table of ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk factors. ...

  8. Coronary Artery Disease - Coronary Heart Disease

    Science.gov (United States)

    ... Tools & Resources Stroke More Coronary Artery Disease - Coronary Heart Disease Updated:May 20,2016 View an animation of ... call 9-1-1. Risk Factors and Coronary Heart Disease Major risk factors that can't be changed ...

  9. Buerger's disease

    International Nuclear Information System (INIS)

    In Buerger's disease, angiographic findings are not pathognomonic, but in most cases they are diagnostic. We reviewed peripheral angiography of 36 cases of Buerger's disease who were suspected clinically during the period from Jan. 1979 to Dec. 1984. The results were as follows: 1. The sex distribution of the cases were 34 males and 2 females (17:1) and most common in 4th decade. Eighty-six percents of the patients were smokers. 2. Chief complaints on admission were ulceration, pain at rest, coldness, and discoloration. 3. The anterior tibial artery was affected most commonly (88%) and posterior tibial (76%), perineal (68%), popliteal (22%), and femoral artery (15%) in order.4. The angiographic findings were 1) In all cases, there was absence of arteriosclerotic lesions and showed smooth vessel walls in non-affected arteries. 2) Direct corkscrew type collaterals were found in 2% of the lesions, and indirect type collaterals in 81%. The tree-root or spider's leg type collaterals were also found in 74%. 3) Standing-wave patterns were found in 30% which affected above the popliteal artery. 4) Early venous drainage was found in 16% of the lesions.

  10. Thyroid diseases

    International Nuclear Information System (INIS)

    This chapter reviews the correlation between thyroid disease, other than cancer, and radiation in the literature. Radiation-induced thyroid disturbance is discussed in the context of external and internal irradiation. External irradiation of 10 to 40 Gy may lower thyroid function several months or years later. Oral administration of I-131 is widely given to patients with Basedow's disease; it may also lower thyroid function with increasing radiation doses. When giving 70 Gy or more of I-131, hypothyroidism has been reported to occur in 20-30% and at least 10%. Thyroiditis induced with internal I-131 irradiation has also been reported, but no data is available concerning external irradiation-induced thyroiditis. The incidence of nodular goiter was found to be several ten times higher with external irradiation than internal irradiation. Thyroid disturbance is correlated with A-bomb survivors. A-bomb radiation can be divided into early radiation within one minute after A-bombing and the subsequent residual radiation. Nodular goiter was significantly more frequent in the exposed group than the non-exposed group; it increased with increasing radiation doses and younger age (20 years or less) at the time of exposure. The incidence of decrease in thyroid function was higher with increasing radiation doses. However, in the case of Nagasaki, the incidence of hypothyroidism was significantly higher in the low-dose exposed group, especially A-bomb survivors aged 10-39 at the time of exposure and women. (N.K.)

  11. [Morton's disease].

    Science.gov (United States)

    Isomoto, Shinji; Tanaka, Yasuhito

    2014-12-01

    Morton's disease refers to neuralgia at the web space of the toes with a pseudo-neuroma. It commonly occurs in the third web space of the foot in middle-aged and older women. The pseudo-neuroma is thought to be a secondary change after entrapment or repeated microtrauma. Patients complain of forefoot pain while walking. Typically, symptoms are caused by tight high-heeled shoes. The physical examination includes palpation of the web spaces and Mulder's test. Weight bearing foot radiographs are used to evaluate the deformity of the foot, especially at metatarsophalangeal (MTP) joints. MRI is useful for differential diagnosis of pseudo-neuroma, MTP joint arthritis, and interdigital bursitis. Conservative treatments are shoe modification, use of orthotic insoles, and injection of corticosteroids and local anesthesia. The injections are useful not only for the treatment but also for diagnosis of Morton's disease. If the local injection is not temporally effective, surgical treatment is not indicated. If the conservative treatment fails, surgical treatment is indicated. The most common surgery is excision of the pseudo-neuroma. The surgery is usually performed using a dorsal approach. PMID:25475032

  12. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  13. Diseases of the skull

    International Nuclear Information System (INIS)

    Different forms of skull diseases viz. inflammatory diseases, skull tumors, primary and secondary bone tumors, are considered. Roentgenograms in some above-mentioned diseases are presented and analysed

  14. [Pancreatic Diseases].

    Science.gov (United States)

    Schöfl, Rainer

    2016-06-22

    The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted. PMID:27329710

  15. Disease Outbreak News

    Science.gov (United States)

    ... and response operations Diseases Biorisk reduction Disease Outbreak News (DONs) Latest DONs 26 August 2016 Middle East ... Disease outbreaks by country RSS feeds Disease outbreak news Announcement: WHO to change the way it reports ...

  16. Alzheimer's Disease Genetics

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Genetics Fact Sheet The Genetics of Disease ...

  17. About Alzheimer's Disease: Treatment

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Treatment How is Alzheimer's disease treated? What ... being researched? What are clinical trials? How is Alzheimer's disease treated? Alzheimer's disease is complex, and it ...

  18. Poorly Responsive Celiac Disease

    Science.gov (United States)

    ... Celiac Disease › Poorly Responsive Celiac Disease Poorly Responsive Celiac Disease It is estimated that up to 20% of ... continuing to ingest gluten. Causes of Poorly Responsive Celiac Disease Continuing Gluten Ingestion The most common reason for ...

  19. Heart disease and women

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007188.htm Heart disease and women To use the sharing features on ... please enable JavaScript. People often do not consider heart disease a woman's disease. Yet cardiovascular disease is the ...

  20. Learning about Your Disease

    Science.gov (United States)

    ... your disease Email this page Print this page Learning about your disease Learn more about common diseases ... may be a treatment option for you. Tweet Learning about your disease Acute Lymphoblastic Leukemia (ALL) Acute ...

  1. Mad Cow Disease

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Mad Cow Disease KidsHealth > For Teens > Mad Cow Disease Print A ... likely are people to get it? What Is Mad Cow Disease? Mad cow disease is an incurable, fatal brain ...

  2. Kidney Disease of Diabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  3. Polycystic Kidney Disease

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  4. Genetics and Rheumatic Disease

    Science.gov (United States)

    ... Well with Rheumatic Disease Genetics and Rheumatic Disease Genetics and Rheumatic Disease Fast Facts Studying twins has ... percent, and for non-identical pairs, even lower. Genetics and ankylosing spondylitis Each rheumatic disease has its ...

  5. Lyme Disease (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Lyme Disease KidsHealth > For Parents > Lyme Disease Print A ... Pacific Northwest, and the northern Midwest states. About Lyme Disease Lyme disease is caused by the bacterium ...

  6. Mitral Valve Disease

    Science.gov (United States)

    ... Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that are ... Transplantation End-stage Lung Disease Adult Lung Transplantation Pediatric Lung ... Aortic Aneurysm Mitral Valve Disease Overview The mitral valve is ...

  7. Acid Lipase Disease

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage Disease, ... Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs when ...

  8. Prion Diseases as Transmissible Zoonotic Diseases

    OpenAIRE

    Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

    2013-01-01

    Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt–Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first r...

  9. Osler's disease

    International Nuclear Information System (INIS)

    Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes and often in organs, such as the lungs, liver and brain (arteriovenous malformations AVM). Various types are known. Patients may present with epistaxis. Teleangiectasia can be identified by visual inspection during physical examination of the skin or oral cavity or by endoscopy. Diagnosis is made after clinical examination and genetic testing based on the Curacao criteria. Modern imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI) have become more important as they can depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the use of a contrast agent while other locations including the central nervous system (CNS) usually require administration of contrast agents. Knowledge of possible clinical manifestations in various organs, possible complications and typical radiological presentation is mandatory to enable adequate therapy of these patients. Interventional procedures are becoming increasingly more important in the treatment of HHT patients. (orig.)

  10. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao

    2014-01-01

    Full Text Available Alzheimer Disease (AD is an outcome as well as source of many diseases. Alzheimer is linked with many other diseases like Diabetes type 2, cholesterolemia, hypertension and many more. But how each of these diseases affecting other is still unknown to scientific community. Signaling Pathways of one disease is interlinked with other disease. But to what extent healthy brain is affected when any signaling in human body is disturbed is the question that matters. There is a need of Pathway analysis, Protein-Protein interaction (PPI and the conserved interactome study in AD and linked diseases. It will be helpful in finding the potent drug or vaccine target in conscious manner. In the present research the Protein-Protein interaction of all the proteins involved in Alzheimer Disease is analyzed using ViSANT and osprey tools and pathway analysis further reveals the significant genes/proteins linking AD with other diseases.

  11. Modeling Infectious Diseases

    Science.gov (United States)

    ... Background Information > Modeling Infectious Diseases Fact Sheet Modeling Infectious Diseases Fact Sheet Tagline (Optional) Using computers to prepare ... Content Area Predicting the potential spread of an infectious disease requires much more than simply connecting cities on ...

  12. Alzheimer's Disease Medications

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Medications Fact Sheet Treatment for Mild to ...

  13. Alzheimer's Disease Research Centers

    Science.gov (United States)

    ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Research Centers The National Institute on Aging ... Repository for Alzheimer's Disease ADC Directory Arizona Arizona Alzheimer’s Disease Center/Sun Health Research Institute Eric Reiman, ...

  14. Understanding Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... National Alzheimer's Project Act (NAPA) About ADEAR Understanding Alzheimer's Disease: What You Need to Know Introduction Many ...

  15. About Alzheimer's Disease: Symptoms

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Symptoms Early signs and symptoms Mild Alzheimer's ... more about other early signs of Alzheimer's » Mild Alzheimer's disease As the disease progresses, people experience greater ...

  16. Pediatric Celiac Disease

    Science.gov (United States)

    ... of Pediatric Gastroenterology and Nutrition Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, and ... protein found in wheat, rye, and barley. Pediatric Celiac Disease If your child has celiac disease, consuming gluten ...

  17. Cyanotic heart disease

    Science.gov (United States)

    ... disease URL of this page: //medlineplus.gov/ency/article/001104.htm Cyanotic heart disease ... heart disease refers to a group of many different heart defects that are present at birth (congenital). They result in a low blood oxygen level. ...

  18. Heart Diseases and Disorders

    Science.gov (United States)

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

  19. Hypothyroidism and Heart Disease

    Science.gov (United States)

    ... Hypothyroidism and Heart Disease Fact Sheet Hypothyroidism and Heart Disease January 2014 Download PDFs English Espanol Editors Alan ... hormone. Why does hypothyroidism increase your risk for heart disease? Both thyroid hormones (T4 and T3) are related ...

  20. What Is Vascular Disease?

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  1. Diabetes and Vascular Disease

    Science.gov (United States)

    ... our CEO Board of Directors Scientific Advisory Board History of Vascular Cures Impact Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic ...

  2. Degenerative Nerve Diseases

    Science.gov (United States)

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  3. Alzheimer's Disease Information Page

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Alzheimer's Disease Information Page Table of Contents (click to ... en Español Additional resources from MedlinePlus What is Alzheimer's Disease? Alzheimer's disease (AD) is an age-related, ...

  4. Motor Neuron Diseases

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS Motor Neuron Diseases Fact Sheet See a list of all ... can I get more information? What are motor neuron diseases? The motor neuron diseases (MNDs) are a ...

  5. Spinal Cord Diseases

    Science.gov (United States)

    ... this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such as meningitis and polio Inflammatory diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral ...

  6. Diabetes and Kidney Disease

    Science.gov (United States)

    ... Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Kidney Disease What are my kidneys and ... urine until releasing it through urination. How can diabetes affect my kidneys? Too much glucose , also called ...

  7. Lyme disease (image)

    Science.gov (United States)

    Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...

  8. Adult Still's disease

    Science.gov (United States)

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  9. Other Retinal Diseases

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... affected by retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases. ...

  10. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  11. Parkinson disease - discharge

    Science.gov (United States)

    Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads ... have you take different medicines to treat your Parkinson disease and many of the problems that may ...

  12. Parkinson disease - discharge

    Science.gov (United States)

    Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads to ... have you take different medicines to treat your Parkinson disease and many of the problems that may come ...

  13. Lyme disease (image)

    Science.gov (United States)

    Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a ...

  14. Lung Diseases and Conditions

    Science.gov (United States)

    ... Share this page from the NHLBI on Twitter. Lung Diseases and Conditions Breathing is a complex process. If ... lead to a disease called COPD (chronic obstructive pulmonary disease). COPD prevents proper airflow in and out of ...

  15. Eye Disease Simulations

    Science.gov (United States)

    ... Jobs Home > Eye Health Information > Eye Disease Simulations Eye Disease Simulations Listen Age-Related Macular Degeneration Cataract Diabetic ... information page Back to top Diabetic Retinopathy Diabetic Eye Disease information page Back to top Glaucoma Glaucoma information ...

  16. Sickle Cell Disease

    Science.gov (United States)

    ... in Sickle Cell Disease New supplement from the American Journal of Preventive Medicine describes the state of sickle cell disease related care in the United States. Read Supplement » ... are affected by sickle cell disease. More WEBINAR ...

  17. Sickle Cell Disease

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Is Sickle Cell Disease? Español The term sickle cell disease (SCD) ... common forms of SCD. Some Forms of Sickle Cell Disease Hemoglobin SS Hemoglobin SC Hemoglobin Sβ 0 thalassemia ...

  18. A faster, high resolution, mtPA-GFP-based mitochondrial fusion assay acquiring kinetic data of multiple cells in parallel using confocal microscopy.

    Science.gov (United States)

    Lovy, Alenka; Molina, Anthony J A; Cerqueira, Fernanda M; Trudeau, Kyle; Shirihai, Orian S

    2012-01-01

    Mitochondrial fusion plays an essential role in mitochondrial calcium homeostasis, bioenergetics, autophagy and quality control. Fusion is quantified in living cells by photo-conversion of matrix targeted photoactivatable GFP (mtPAGFP) in a subset of mitochondria. The rate at which the photoconverted molecules equilibrate across the entire mitochondrial population is used as a measure of fusion activity. Thus far measurements were performed using a single cell time lapse approach, quantifying the equilibration in one cell over an hour. Here, we scale up and automate a previously published live cell method based on using mtPAGFP and a low concentration of TMRE (15 nm). This method involves photoactivating a small portion of the mitochondrial network, collecting highly resolved stacks of confocal sections every 15 min for 1 hour, and quantifying the change in signal intensity. Depending on several factors such as ease of finding PAGFP expressing cells, and the signal of the photoactivated regions, it is possible to collect around 10 cells within the 15 min intervals. This provides a significant improvement in the time efficiency of this assay while maintaining the highly resolved subcellular quantification as well as the kinetic parameters necessary to capture the detail of mitochondrial behavior in its native cytoarchitectural environment. Mitochondrial dynamics play a role in many cellular processes including respiration, calcium regulation, and apoptosis. The structure of the mitochondrial network affects the function of mitochondria, and the way they interact with the rest of the cell. Undergoing constant division and fusion, mitochondrial networks attain various shapes ranging from highly fused networks, to being more fragmented. Interestingly, Alzheimer's disease, Parkinson's disease, Charcot Marie Tooth 2A, and dominant optic atrophy have been correlated with altered mitochondrial morphology, namely fragmented networks. Often times, upon fragmentation

  19. Diabetes and kidney disease

    Science.gov (United States)

    Diabetic nephropathy; Nephropathy - diabetic; Diabetic glomerulosclerosis; Kimmelstiel-Wilson disease ... Diabetic kidney disease is a major cause of sickness and death in people with diabetes. It can ...

  20. Genetics and Neuromuscular Diseases

    Science.gov (United States)

    ... Dermatomyositis Inclusion-body myositis Diseases of Neuromuscular Junction Myasthenia gravis Lambert-Eaton (myasthenic) syndrome Congenital myasthenic syndromes Diseases of Peripheral Nerve Charcot-Marie- ...

  1. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  2. Parasitic diseases of lungs

    International Nuclear Information System (INIS)

    Roentgenologic semiotics of the main parasitic diseases of lungs is described: echinococcosis, paragonimiasis, cysticercosis, toxoplasmosis, ascariasis, amebiosis and some rarely met parasitic diseases

  3. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  4. What Causes Heart Disease?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Heart Disease? Research suggests that coronary heart disease (CHD) begins with damage to the lining and ... causing coronary microvascular disease (MVD). Coronary MVD is heart disease that affects the heart's tiny arteries. The cause ...

  5. What Is Crohn's Disease

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Crohn's Disease What is Crohn's Disease Past Issues / Winter 2016 Table of Contents As ... large intestine, leading to the anus. Who Gets Crohn's Disease? Both men and women can get Crohn's disease, ...

  6. Small animal disease surveillance: respiratory disease

    OpenAIRE

    Sánchez-Vizcaíno, Fernando; Daly, Janet M.; Philip H Jones; Dawson, Susan; Gaskell, Rosalind; Menacere, Tarek; Heayns, Bethaney; Wardeh, Maya; Newman, Jenny; Everitt, Sally; Day, Michael J.; McConnell, Katie; Noble, Peter J.M.; Radford, Alan D

    2016-01-01

    This second Small Animal Disease Surveillance report focuses on syndromic surveillance of i) respiratory disease in veterinary practice and ii) feline calicivirus (FCV) based on laboratory diagnosis, in a large veterinary-visiting pet population of the UK between January 2014 and December 2015. Presentation for respiratory disease comprised 1.7%, 2.3% and 2.5% of canine, feline and rabbit consultations, respectively. In dogs, the most frequent respiratory sign reported was coughing (71.1% of ...

  7. Lyme Disease and Pregnancy

    OpenAIRE

    Alexander, James M.; Cox, Susan M.

    1995-01-01

    Lyme disease is the most commonly transmitted vector-borne disease in the United States, with many regions of the country at risk. Like other spirochete-borne infections, Lyme disease progresses in stages, making diagnosis in the early stages of the illness and prompt treatment important for cure. An early diagnosis is made difficult by the less-than-ideal serologic tests and the varied clinical presentations of the disease. Although Lyme disease has been reported in pregnancy, the transmissi...

  8. Pregnancy and periodontal disease

    OpenAIRE

    Sağlam, Ebru; SARUHAN, Nesrin; Çanakçı, Cenk Fatih

    2015-01-01

    Some maternal immunological changes due to pregnancy increases susceptibility to infections. Periodontal disease, the main cause is plaque, is a common disease which is seen multifactorial and varying severity. There are many clinical criteria for diagnosis of periodontal disease. Correlation between pregnancy and periodontal inflammation is known for many years. Periodontal disease affects pregnant’s systemic condition and also has negative effects on fetus. Periodontal disease increases the...

  9. Hyperparathyroidism of Renal Disease

    Science.gov (United States)

    Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J

    2016-01-01

    Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, disease. PMID:27479950

  10. Renal cystic disease

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, D.S.

    1988-01-01

    The book begins with an overview of renal cystic disease and a presentation of simple renal cysts. Subsequent chapters cover cystic disease in association with renal neoplasms and medullary sponge kidney. The chapters addressing autosomal-dominant and autosomal-recessive polycystic kidney disease discuss and differentiate the infantile and adult forms of the disease. There are also separate discussions of medullary cystic disease, multicystic dysplastic kidney, and cysts of the renarenal sinus.

  11. Treating neglected tropical diseases

    OpenAIRE

    Director: Mectizan Donation Program, Georgia, USA. www.mectizan.org

    2013-01-01

    The name neglected tropical diseases (NTDs) covers a range of diseases that cause disability, early death, and slowed physical and mental development. The first two in entries Table 1 are diseases that cause blindness. These diseases of neglected and impoverished peoples maintain a cycle of poverty and delayed development of the populations affected. The diseases themselves have been neglected in the push to control malaria, TB and AIDS.

  12. Prion diseases as transmissible zoonotic diseases.

    Science.gov (United States)

    Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

    2013-02-01

    Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt-Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea. PMID:24159531

  13. About Alzheimer's Disease: Alzheimer's Basics

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Alzheimer's Basics What is Alzheimer's disease? What happens to ... with Alzheimer's disease? What is dementia? What is Alzheimer's disease? Alzheimer’s disease is an irreversible, progressive brain ...

  14. Hereditary motor and sensory neuropathy with congenital glaucoma: report on a family Neuropatia hereditária sensitivo-motora com glaucoma congênito: descrição de uma família

    Directory of Open Access Journals (Sweden)

    WALTER O. ARRUDA

    1999-06-01

    Full Text Available We report three siblings of a family with hereditary motor and sensory polyneuropathy (HMSN and buphthalmos. Electrophysiological studies showed a demyelinating neuropathy and pathological findings showed severe loss of myelinated fibers (MF, thin myelin sheaths and myelin infoldings in a few remaining MF. The presumed mode of inheritance is autosomal recessive. This family probably represents an unique form of CMT4 that may be related to one of the congenital glaucoma genic locus, particularly GLC3A and GLC3B, described in Turkish families.Descrevemos três membros afetados de uma família com neuropatia hereditária sensitivo-motora tipo I (desmielinizante e glaucoma congênito (buftalmia. O estudo eletrofisiológico dos membros afetados demonstrou polineuropatia sensitivo-motora desmielinizante, com ausência ou redução acentuada das velocidades de neurocondução sensitiva e motora. A biópsia do nervo sural revelou redução moderada a grave das fibras mielinizadas, bainhas de mielina de espessura diminuída (remielinização com dobramentos delas nas poucas fibras mielinizadas remanescentes. Não foram observadas formações em casca de cebola, nem tampouco alterações hipertróficas. O padrão de herança desta família parece ser autossômico recessivo. Sugerimos tratar-se de uma forma singular de doença de Charcot-Marie-Tooth autossômica recessiva (CMT4, que eventualmente pode possuir locus gênico próximo a um dos locus do glaucoma congênito (GLC3A e GLC3B, localizados nos cromossomos 2p21 e 1p36.

  15. Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.

    Science.gov (United States)

    Auer-Grumbach, Michaela; Toegel, Stefan; Schabhüttl, Maria; Weinmann, Daniela; Chiari, Catharina; Bennett, David L H; Beetz, Christian; Klein, Dennis; Andersen, Peter M; Böhme, Ilka; Fink-Puches, Regina; Gonzalez, Michael; Harms, Matthew B; Motley, William; Reilly, Mary M; Renner, Wilfried; Rudnik-Schöneborn, Sabine; Schlotter-Weigel, Beate; Themistocleous, Andreas C; Weishaupt, Jochen H; Ludolph, Albert C; Wieland, Thomas; Tao, Feifei; Abreu, Lisa; Windhager, Reinhard; Zitzelsberger, Manuela; Strom, Tim M; Walther, Thomas; Scherer, Steven S; Züchner, Stephan; Martini, Rudolf; Senderek, Jan

    2016-09-01

    Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment. PMID:27588448

  16. Chronic granulomatous disease

    Science.gov (United States)

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called ... some types of bacteria and fungi. This disorder leads to long- ...

  17. Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Creutzfeldt-Jakob disease (CJD) is a rare, degenerative brain disorder. Symptoms usually start around age 60. Memory problems, behavior changes, vision ... during a medical procedure Cattle can get a disease related to CJD called bovine spongiform encephalopathy (BSE) ...

  18. Kennedy's Disease Association

    Science.gov (United States)

    ... of great accomplishments. It is passed on from generation to generation in families worldwide. Males generally inherit the disease ... on the picture above. Spinal Bulbar Muscular Atrophy , X-linked Spinal Bulbar Muscular Atrophy, SBMA, neuromuscular disease, ...

  19. Cat Scratch Disease

    Science.gov (United States)

    Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry the infection ... symptoms of CSD, call your doctor. Centers for Disease Control and Prevention

  20. Pelvic Inflammatory Disease

    Science.gov (United States)

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  1. Tay-Sachs Disease

    Science.gov (United States)

    Tay-Sachs disease is a rare, inherited disorder. It causes too much of a fatty substance to build up in the ... mental and physical problems. Infants with Tay-Sachs disease appear to develop normally for the first few ...

  2. Carotid Artery Disease

    Science.gov (United States)

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  3. Lewy Body Disease

    Science.gov (United States)

    Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss of mental ... to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build ...

  4. Peripheral Arterial Disease

    Science.gov (United States)

    Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...

  5. Sickle Cell Disease Quiz

    Science.gov (United States)

    ... About Us Information For... Media Policy Makers Sickle Cell Disease Quiz Language: English Español (Spanish) Recommend on ... True or False: Only African Americans get sickle cell disease. A True B False 2. True or ...

  6. Celiac disease - sprue

    Science.gov (United States)

    ... Addison's disease Down syndrome Intestinal cancer Intestinal lymphoma Lactose intolerance Thyroid disease Type 1 diabetes ... unchanged) Diarrhea , either constant or off and on Lactose intolerance (common when the person is diagnosed, usually goes ...

  7. Heart disease - risk factors

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000106.htm Heart disease - risk factors To use the sharing features on ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. Changing ...

  8. Gastroesophageal Reflux Disease (GERD)

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Gastroesophageal Reflux Disease (GERD) KidsHealth > For Teens > Gastroesophageal Reflux Disease (GERD) Print ... healthy teens can have GERD, too. What Is GERD? Gastroesophageal (pronounced: gas-tro-ih-sah-fuh-JEE- ...

  9. Collagen vascular disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this page, ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many of many ...

  10. HIV and Kidney Disease

    Science.gov (United States)

    ... Sheets Permission to Use Fact Sheets Sponsors and Advertising Privacy Policy Project ... Disease WHY SHOULD PEOPLE WITH HIV CARE ABOUT KIDNEY DISEASE? WHAT IS NORMAL KIDNEY FUNCTION? HOW DO I KNOW IF THERE ARE PROBLEMS ...

  11. Creutzfeldt-Jakob Disease

    Science.gov (United States)

    ... TDP43-related Dementia 2013 Andrew Watt Characterisation of Tau Imaging Ligands for Alzheimer's Disease and other Dementias 2010 Marco Prado The Prion Protein as a Therapeutic Target in Alzheimer's Disease 2007 ...

  12. Parkinson's Disease Dementia

    Science.gov (United States)

    ... TDP43-related Dementia 2013 Andrew Watt Characterisation of Tau Imaging Ligands for Alzheimer's Disease and other Dementias 2010 Marco Prado The Prion Protein as a Therapeutic Target in Alzheimer's Disease 2007 ...

  13. Autoimmune Inner Ear Disease

    Science.gov (United States)

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  14. Celiac disease - nutritional considerations

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002443.htm Celiac disease - nutritional considerations To use the sharing features on this page, please enable JavaScript. Celiac disease is an immune disorder passed down through families. ...

  15. Cardiovascular Disease and Diabetes

    Science.gov (United States)

    ... Blood Pressure Tools & Resources Stroke More Cardiovascular Disease & Diabetes Updated:Mar 23,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  16. Lyme Disease Tests

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Lyme Disease Tests Share this page: Was this page helpful? ... else I should know? How is it used? Lyme disease tests are used to determine if a person ...

  17. Lung disease - resources

    Science.gov (United States)

    ... gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html Emphysema/COPD (Chronic Obstructive Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and ...

  18. Occlusive Peripheral Arterial Disease

    Science.gov (United States)

    ... erythrocyte sedimentation rate (ESR) and level of C-reactive protein, which is produced only when inflammation is present. ... people with occlusive peripheral arterial disease also have coronary artery disease. Amputation of a limb may be necessary if ...

  19. About Alzheimer's Disease: Causes

    Science.gov (United States)

    ... Project Act (NAPA) About ADEAR About Alzheimer's Disease: Causes Age-related changes in the brain Genetics Health, ... for the Causes of AD" NIA Information on Causes Alzheimer’s Disease in People with Down Syndrome Understanding ...

  20. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  1. Parkinson's Disease Foundation

    Science.gov (United States)

    ... the disease. Learn More A New Home for Parkinson's Science An open access journal, enabling professionals and ... Contact the HelpLine Parkinson's News Upcoming Events National Parkinson Foundation (NPF) and the Parkinson's Disease Foundation (PDF) ...

  2. What Is Parkinson's Disease?

    Science.gov (United States)

    ... National HelpLine Educational Publications Online Seminars Parkinson's News Parkinson's HelpLine Learn More Educational Materials Do you want ... resources & more. Order Free Materials Today What is Parkinson’s Disease? Parkinson's disease (PD) is a chronic and ...

  3. Managing Your Parkinson's Disease

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  4. Parkinson's Disease Foundation Newsletter

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  5. Lyme Disease Data

    Science.gov (United States)

    ... Lyme disease FAQ Health care providers Educational materials Data and Statistics Recommend on Facebook Tweet Share Compartir ... in the northeast and upper Midwest. Lyme Disease Data File To facilitate the public health and research ...

  6. Gum Disease in Children

    Science.gov (United States)

    ... Find a Periodontist Gum Disease In Children Chronic gingivitis. aggressive periodontitis and generalized aggressive periodontitis are types ... children. Types of periodontal diseases in children Chronic gingivitis is common in children. It usually causes gum ...

  7. Diabetic Eye Disease

    Science.gov (United States)

    ... we see Common vision problems Age-Related Eye Diseases Eye Health Tips Podcasts Text Messages Vision-Related Terms, ... los Ojos Cómo hablarle a su oculista Diabetic Eye Disease Listen View this module and educate yourself, family, ...

  8. Learning about Huntington's Disease

    Science.gov (United States)

    ... Mouse Models Of Huntington's Disease 1998 News Release Learning About Huntington's Disease What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Huntington's Outreach ...

  9. Pregnancy and Thyroid Disease

    Science.gov (United States)

    ... Disease Organizations (PDF, 269 KB). Alternate Language URL Pregnancy and Thyroid Disease Page Content On this page: ... responds by decreasing TSH production. [ Top ] How does pregnancy normally affect thyroid function? Two pregnancy-related hormones— ...

  10. Celiac disease - sprue

    Science.gov (United States)

    ... Addison disease Down syndrome Intestinal cancer Intestinal lymphoma Lactose intolerance Thyroid disease Type 1 diabetes Symptoms The symptoms ... unchanged) Diarrhea , either constant or off and on Lactose intolerance (common when the person is diagnosed, often goes ...

  11. Tay-Sachs Disease

    Science.gov (United States)

    Tay-Sachs disease is a rare, inherited disorder. It causes too much of a fatty substance to build ... cells, causing mental and physical problems. Infants with Tay-Sachs disease appear to develop normally for the first ...

  12. Cat scratch disease (image)

    Science.gov (United States)

    Cat scratch disease is an infectious illness associated with cat scratches, bites, or exposure to cat saliva, causing chronic swelling of the lymph nodes. Cat scratch disease is possibly the most common cause of ...

  13. Myonecrosis of Behcet's disease

    International Nuclear Information System (INIS)

    Behcet's disease is an inflammatory disease of unknown cause characterized by intermittent episodes of acute inflammation manifested by oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. We report a rare case of myonecrosis associated with Behcet's disease. Myonecrosis of Behcet's disease can mimic soft tissue abscess and therefore awareness of this entity in the appropriate clinical setting is important for initiation of appropriate and timely treatment. (orig.)

  14. Endemic treponemal diseases.

    OpenAIRE

    Marks, M; Solomon, AW; Mabey, DC

    2014-01-01

    : The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecologic...

  15. Self Inflicted Dermatological Diseases

    Directory of Open Access Journals (Sweden)

    Ertuğrul H. Aydemir

    2010-07-01

    Full Text Available This group of diseases are characterised with the aggravated types of stress releasing behaviors like scratching, picking, squeezing, and sucking. Lichen simplex chronicus, prurigo nodularis, neurotic excoriations, trichotillomani, and onychotillomani are the diseases in this group. Depression, anxiety, and obsesif compulsive disease are the main underlying psychologic diseases. They need a skillfull psychiatric approach in addition to dermatologic treatment, and should be treated with patience in a long duration.

  16. Self Inflicted Dermatological Diseases

    OpenAIRE

    Ertuğrul H. Aydemir

    2010-01-01

    This group of diseases are characterised with the aggravated types of stress releasing behaviors like scratching, picking, squeezing, and sucking. Lichen simplex chronicus, prurigo nodularis, neurotic excoriations, trichotillomani, and onychotillomani are the diseases in this group. Depression, anxiety, and obsesif compulsive disease are the main underlying psychologic diseases. They need a skillfull psychiatric approach in addition to dermatologic treatment, and should be treated with patien...

  17. Lyme Disease and Oncothermia

    OpenAIRE

    2013-01-01

    Lyme disease is a tick-borne disease with multiple organ failures, and systemic disorders. Dramatic change becomes apparent in the chronic phase of the disease. Chronic fatigue syndrome, lapse of concentration, depression, joint pain, and muscle pain are a few, but major clinical symptoms characterizing the disease. The human immune system is defenseless. Borrelia uses various mechanisms to escape from immunoattacks or antibiotic therapies. This “stealth phenomenon” needs new therapeutic prin...

  18. Caroli disease and cholangiocarcinoma

    OpenAIRE

    Sezer, Semih; TAYFUR, Öykü; ŞENGÜL, Ayşegül; ÖZİN, Yasemin; Parlak, Erkan; KAÇAR, Sabite; OĞUZ, Dilek; Şaşmaz, Nurgül

    2009-01-01

    Caroli's disease is a congenital disorder characterized by focal and/or diffuse cystic dilatation of intrahepatic bile ducts. These patients have increased incidence of bile duct stones, recurrent cholangitis attacks and cholangiocarcinoma risk. Caroli's disease rarely metastasizes to distant sites. Treatment depends on the localization and extent of the disease. Cholangiocellular carcinoma developing from an underlying Caroli's disease is difficult to diagnose with various imaging techniques...

  19. Iron and Liver Diseases

    OpenAIRE

    Fargion, Silvia; Mattioli, Michela; Fracanzani, Anna Ludovica; Fiorelli, Gemino

    2000-01-01

    A mild to moderate iron excess is found in patients with liver diseases apparently unrelated to genetic hemochromatosis. Iron appears to affect the natural history of hepatitis C virus-related chronic liver diseases, alcoholic liver disease and nonalcoholic steatohepatitis by leading to a more severe fibrosis and thus aiding the evolution to cirrhosis.Ahigher frequency of mutations of the HFE gene, the gene responsible for hereditary hemochromatosis, is found in patients with liver diseases a...

  20. Parkinson's disease and anxiety

    OpenAIRE

    Walsh, K; Bennett, G

    2001-01-01

    There has been a recent surge of interest in the subject of anxiety in patients with Parkinson's disease. Up to 40% of patients with Parkinson's disease experience clinically significant anxiety. This anxiety may be a psychological reaction to the stress of the illness or may be related to the neurochemical changes of the disease itself. Antiparkinsonian drugs may have a role in the pathogenesis of the anxiety. The anxiety disorders in Parkinson's disease patients appear to be clustered in th...

  1. Methamphetamine and Parkinson's Disease

    OpenAIRE

    Noelia Granado; Sara Ares-Santos; Rosario Moratalla

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to t...

  2. Heart Disease in Women

    Science.gov (United States)

    ... States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing or ... the heart itself. This is called coronary artery disease, and it happens slowly over time. It's the ...

  3. Overview of Infectious Diseases

    Science.gov (United States)

    ... Español Text Size Email Print Share Overview of Infectious Diseases Page Content Article Body I nfectious diseases are ... worms Last Updated 11/21/2015 Source Immunizations & Infectious Diseases: An Informed Parent's Guide (Copyright © 2006 American Academy ...

  4. Heart Disease in Women

    Science.gov (United States)

    ... United States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing or ... It's the major reason people have heart attacks. Heart diseases that affect women more than men include Coronary ...

  5. Menopause and Heart Disease

    Science.gov (United States)

    ... Blood Pressure Tools & Resources Stroke More Menopause and Heart Disease Updated:Apr 18,2016 Heart disease risk rises for everyone as they age, but ... women is seen about 10 years after menopause. Heart disease is the leading killer of women . Estrogen Levels ...

  6. Living with Heart Disease

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With Heart Disease If you have coronary heart disease (CHD), you can take steps to control its ... the section of this article titled "How Is Heart Disease Treated?" You also can visit the Health Topics ...

  7. Heart Disease in Women

    Science.gov (United States)

    ... heart disease risk factors causes coronary MVD. Although death rates from heart disease have dropped in the last 30 years, they ... stopped her "dead in her tracks." Jennifer reminds us how heart disease takes too many of our moms, sisters, and ...

  8. Metastatic Crohn's disease

    Science.gov (United States)

    Lanka, Padmavathy; Lanka, Lakshmana Rao; Sylvester, N.; Lakshmi, M. Dhana; Ethirajan, N.

    2014-01-01

    Crohn's disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn's disease (CCD) is synonymous with metastatic Crohn's disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity. PMID:24616854

  9. Metastatic Crohn's disease

    OpenAIRE

    Padmavathy Lanka; Lakshmana Rao Lanka; Sylvester, N.; M Dhana Lakshmi; Ethirajan, N.

    2014-01-01

    Crohn′s disease, first described in 1922, is characterized by segmental granulomatous inflammation of the intestinal tract and frequently involves the cutaneous tissues as well. Cutaneous Crohn′s disease (CCD) is synonymous with metastatic Crohn′s disease (MSD). A case of CCD, without any gastrointestinal involvement is reported for its rarity.

  10. [Fatigue in neuromuscular disease

    NARCIS (Netherlands)

    Engelen, B.G.M. van; Kalkman, J.S.; Schillings, M.L.; Werf, S.P. van der; Bleijenberg, G.; Zwarts, M.J.

    2004-01-01

    Chronic fatigue is a symptom of diseases such as cancer, multiple sclerosis, Parkinson's and cerebrovascular disease. Fatigue can also be present in people with no demonstrable somatic disease. If certain criteria are met, chronic-fatigue syndrome may be diagnosed in these cases. Fatigue is a multi-

  11. Childhood Contagious Diseases

    Science.gov (United States)

    ... these diseases are so common in children. Contagious diseases are often caused by the spread of bacteria (such as in scarlet fever) or viruses (such as in chickenpox, measles, hand-foot-and-mouth disease, and quite a few others) in droplets of ...

  12. Heart Disease Risk Factors

    Science.gov (United States)

    ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke Heart Disease Risk Factors Recommend ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke File Formats Help: How do ...

  13. Sickle Cell Disease

    Science.gov (United States)

    ... sickle cell disease? Sickle cell disease, also called sickle cell anemia, is a hereditary condition (which means it runs ... or blocks blood and oxygen reaching nearby tissues. Sickle cell disease ... the whites of the eyes) Anemia (the decreased ability of the blood to carry ...

  14. Peripheral Artery Disease

    Science.gov (United States)

    ... or atherectomy may be used to help improve blood flow. What is peripheral artery disease (PAD)? How is peripheral artery disease evaluated? How ... PAD are diabetes, smoking, high cholesterol and high blood pressure. Most cases occur in ... is peripheral artery disease evaluated? Several imaging tests can be used to ...

  15. Living with Crohn's Disease

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Crohn's Disease Living with Crohn's Disease Past Issues / Winter 2016 Table of Contents Photo ... Why have you chosen to speak out about Crohn's disease? For many years I really didn't talk ...

  16. What Is Crohn's Disease?

    Science.gov (United States)

    ... What are Crohn's & Colitis? > What is Crohn’s Disease? Crohn’s Disease is a Chronic Condition By understanding your body ... live a full and rewarding life What is Crohn’s Disease? Email Print + Share Named after Dr. Burrill B. ...

  17. Learning about Parkinson's Disease

    Science.gov (United States)

    ... suggest that these genes are also involved in early-onset Parkinson's disease (diagnosed before the age of 30) or ... LRRK2 causes Parkinson's Disease [interscience.wiley.com] Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1 [sciencemag.org] ...

  18. Candidate parasitic diseases.

    OpenAIRE

    Behbehani, K

    1998-01-01

    This paper discusses five parasitic diseases: American trypanosomiasis (Chagas disease), dracunculiasis, lymphatic filariasis, onchocerciasis and schistosomiasis. The available technology and health infrastructures in developing countries permit the eradication of dracunculiasis and the elimination of lymphatic filariasis due to Wuchereria bancrofti. Blindness due to onchocerciasis and transmission of this disease will be prevented in eleven West African countries; transmission of Chagas dise...

  19. Glycation in Parkinson's disease and Alzheimer's disease.

    Science.gov (United States)

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  20. Genetics Home Reference: Parkinson disease

    Science.gov (United States)

    ... links) LRRK2-Related Parkinson Disease Parkin Type of Early-Onset Parkinson Disease Parkinson Disease Overview PINK1 Type of Young- ... Parkinson disease 5 Parkinson disease 6, autosomal recessive early-onset Parkinson disease 7 Parkinson disease 8, autosomal dominant Parkinson ...

  1. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  2. Radiotherapy of benign diseases

    International Nuclear Information System (INIS)

    Still today radiotherapy is of decisive relevance for several benign diseases. The following ones are briefly described in this introductory article: 1. Certain inflammatory and degenerative diseases as furuncles in the face, acute thrombophlebitis, recurrent sudoriparous abscesses, degenerative skeletal diseases, cervical syndrome and others; 2. rheumatic joint diseases; 3. Bechterew's disease; 4. primary presenile osteoporosis; 5. synringomyelia; 6. endocrine ophthalmopathy; 7. hypertrophic processes of the connective tissue; 8. hemangiomas. A detailed discussion and a profit-risk analysis is provided in the individual chapters of the magazine. (MG)

  3. Disease: H00061 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00061 Prion diseases; Creutzfeldt-Jacob disease (CJD); Gerstmann-Straussler diseas...e (GSD); Gerstmann-Straussler-Scheinker disease (GSSD); Fatal familial insomnia (FFI) Prion diseases, also t...ermed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that... affect humans and a number of other animal species. The etiology of these diseases...vely folded protein, PrPC. Neurodegenerative disease hsa05020 Prion diseases PRNP (mutation) [HSA:5621] [KO:

  4. Fight against infectious diseases.

    Science.gov (United States)

    Soda, K; Kamakura, M; Kitamura, K

    1996-08-01

    During early Meiji era in Japan, there were frequent epidemics of fatal acute communicable diseases such as cholera, dysentery and smallpox, and preventive measures and preparations for acute infectious diseases were urgently needed. Together with improvement of scientific preparations, the Communicable Disease Prevention Law was promulgated in 1897. Then gradually until 1940's, the focus of preventive measures have been shifted from acute infectious diseases to chronic ones, particularly tuberculosis. After the World War II, except the short period of social confusion, major legally-defined communicable diseases had been decreasing rapidly mainly due to the use of antibiotics and improvement of environmental sanitation. At the same time, the introduction of preventive vaccination marked a new era for the prevention of infectious diseases and was largely responsible for the remarkable decrease of infant mortality in Japan. Recently the concept of defense by vaccination against infectious diseases has evolved from group-oriented to individual-oriented, so that the Preventive Vaccination Law was drastically revised in 1994. Currently, effective counter-measures against newly emerged infectious diseases, as viral hepatitis, institution-acquired infection, viral hemorrhagic fever etc., have been implemented. For the future, improvement of infections disease surveillance, vaccine development and expansion of vaccination coverage along with monitoring side-effects, preventive health education on AIDS/STDs, addressing the special needs of foreigners living in Japan and international collaboration for disease control abroad are all vital to the success of protection of the public's health from infectious diseases in Japan. PMID:8800275

  5. Diagnosis of Pompe disease

    DEFF Research Database (Denmark)

    Vissing, John; Lukacs, Zoltan; Straub, Volker

    2013-01-01

    The diagnosis of Pompe disease (acid maltase deficiency, glycogen storage disease type II) in children and adults can be challenging because of the heterogeneous clinical presentation and considerable overlap of signs and symptoms found in other neuromuscular diseases. This review evaluates some of...... the methods used in the diagnosis and differential diagnosis of late-onset Pompe disease. Muscle biopsy is commonly used as an early diagnostic tool in the evaluation of muscle disease. However, experience has shown that relying solely on visualizing a periodic acid-Schiff-positive vacuolar myopathy...... to identify late-onset Pompe disease often leads to false-negative results and subsequent delays in identification and treatment of the disorder. Serum creatine kinase level can be normal or only mildly elevated in late-onset Pompe disease and is not very helpful alone to suggest the diagnosis, but...

  6. Celiac disease and autoimmune thyroid disease.

    Science.gov (United States)

    Ch'ng, Chin Lye; Jones, M Keston; Kingham, Jeremy G C

    2007-10-01

    Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It

  7. Genetics of Proteasome Diseases

    Directory of Open Access Journals (Sweden)

    Aldrin V. Gomes

    2013-01-01

    Full Text Available The proteasome is a large, multiple subunit complex that is capable of degrading most intracellular proteins. Polymorphisms in proteasome subunits are associated with cardiovascular diseases, diabetes, neurological diseases, and cancer. One polymorphism in the proteasome gene PSMA6 (−8C/G is associated with three different diseases: type 2 diabetes, myocardial infarction, and coronary artery disease. One type of proteasome, the immunoproteasome, which contains inducible catalytic subunits, is adapted to generate peptides for antigen presentation. It has recently been shown that mutations and polymorphisms in the immunoproteasome catalytic subunit PSMB8 are associated with several inflammatory and autoinflammatory diseases including Nakajo-Nishimura syndrome, CANDLE syndrome, and intestinal M. tuberculosis infection. This comprehensive review describes the disease-related polymorphisms in proteasome genes associated with human diseases and the physiological modulation of proteasome function by these polymorphisms. Given the large number of subunits and the central importance of the proteasome in human physiology as well as the fast pace of detection of proteasome polymorphisms associated with human diseases, it is likely that other polymorphisms in proteasome genes associated with diseases will be detected in the near future. While disease-associated polymorphisms are now readily discovered, the challenge will be to use this genetic information for clinical benefit.

  8. Coeliac disease and epilepsy.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Whether there is an association between coeliac disease and epilepsy is uncertain. Recently, a syndrome of coeliac disease, occipital lobe epilepsy and cerebral calcification has been described, mostly in Italy. We measured the prevalence of coeliac disease in patients attending a seizure clinic, and investigated whether cerebral calcification occurred in patients with both coeliac disease and epilepsy. Screening for coeliac disease was by IgA endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. Of 177 patients screened, four patients were positive. All had small-bowel histology typical of coeliac disease. The overall frequency of coeliac disease in this mixed patient sample was 1 in 44. In a control group of 488 pregnant patients, two serum samples were positive (1 in 244). Sixteen patients with both coeliac disease and epilepsy, who had previously attended this hospital, were identified. No patient had cerebral calcification on CT scanning. Coeliac disease appears to occur with increased frequency in patients with epilepsy, and a high index of suspicion should be maintained. Cerebral calcification is not a feature of our patients with epilepsy and coeliac disease, and may be an ethnically-or geographically-restricted finding.

  9. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco

    2015-12-01

    Full Text Available Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

  10. Multiple cystic lung disease.

    Science.gov (United States)

    Ferreira Francisco, Flavia Angélica; Soares Souza, Arthur; Zanetti, Gláucia; Marchiori, Edson

    2015-12-01

    Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management. PMID:26621970

  11. Disease: H01077 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ts or patients with underlying disease. Infectious disease Bordetella hinzii Amoxic... the genus Bordetella that is isolated from poultry with respiratory disease. B. hinzii may cause disease in immunocompromised patien

  12. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  13. Mad Cow Disease (For Parents)

    Science.gov (United States)

    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Mad Cow Disease KidsHealth > For Parents > Mad Cow Disease Print A ... Contagious? What Is Being Done About It About Mad Cow Disease Mad cow disease has been in the headlines ...

  14. Genetics Home Reference: prion disease

    Science.gov (United States)

    ... as bovine spongiform encephalopathy (BSE) or, more commonly, "mad cow disease." Another example of an acquired human prion disease ... forms of prion disease , including kuru and variant Creutzfeldt-Jakob disease, are not inherited. Related Information What does it ...

  15. Disease: H00921 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available terion to establish the diagnosis. Congenital disorder; Eye disease; Hematologic disease; Skin and connective tissue disea...se; Nervous system disease TINF2 [HSA:26277] [KO:K11112] Dyskeratos

  16. Diabetes, Heart Disease, and Stroke

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  17. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary ... to the liver without cirrhosis. How does liver disease relate to pulmonary hypertension? Liver disease can cause what is known ...

  18. Disease: H01151 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available infections in patients with underlying diseases. Infectious disease Brevundimonas vesicularis Brevundimonas...d-stage renal disease Autoimmune diseases Vancomycin [ATC: J01XA01] Ceftazidime [ATC:J01DD02] Levofloxacin [

  19. Genetics Home Reference: Sandhoff disease

    Science.gov (United States)

    ... links) Health Topic: Degenerative Nerve Diseases Health Topic: Tay-Sachs Disease Genetic and Rare Diseases Information Center (1 ... UK) National Organization for Rare Disorders (NORD) National Tay-Sachs and Allied Diseases Association Genetic Testing Registry (1 ...

  20. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions Alzheimer disease Alzheimer disease Enable Javascript to view the expand/collapse boxes. Print All Open All Close All Description Alzheimer disease is a degenerative disease of the brain ...