Deciphering the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome / 中华肾脏病杂志

Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Genotype and phenotype analysis of children with autosomal dominant inheritance Alport syndrome / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological and gene mutation characteristics of children with autosomal dominant inheritance Alport syndrome (ADAS), and to improve the understanding of ADAS.Methods:Ten children with ADAS diagnosed in the Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2016 to February 2020 were enrolled.The clinicopathological and gene mutation features were retrospectively analyzed, and the patients were followed up.Results:(1) The median age at diagnosis was 5.7 (2.4, 9.8) years.Of 10 children, 6 cases (60.0%) showed a family history of renal failure, 4 cases (40.0%) presented with hematuria and proteinuria at diagnosis, and 2 cases (20.0%) suffered a high-frequency hearing loss.Renal biopsy showed extensive splitting and lamellation of the glomerular basement membrane (GBM) dense layer in 4 cases (40.0%), and segmental splitting and lamellation in 6 cases (60.0%). (2)Among 10 children, 4 cases (40.0%) were heterozygous mutations of COL4A3 gene, including 2 point mutations of glycine, and 2 splicing mutations.The other 6 cases (60.0%) were heterozygous mutations of COL4A4 gene, including collagen glycine point mutations in 4 cases, nonsense mutation in 1 case and large deletion in 1 case.Six mutations were new and never reported before. Conclusions:The early clinical presentations of children with ADAS are often atypical and extrarenal manifestations are less common.The GBM dense layer is mainly featured by segmental splitting and lamellation.Glycine point mutations account for the majority of the gene mutations.

Characteristics of autosomal dominant retinal diseases and gene therapy strategies / 中华实验眼科杂志

Inherited retinal diseases (IRDs), one type of the major eye diseases resulting in blindness, can be caused by more than 270 identified causative genes.The most common form of IRDs is retinitis pigmentosa.There is no generally accepted cure for vision impairment due to IRDs.In recent years, the first gene replacement therapy has been approved for the treatment of autosomal recessive IRDs.Because of the variety of pathogenesis, including gain-of-function and dominant-negative effects in addition to a few loss-of-function mutations, gene replacement therapy of autosomal dominant IRDs is not always effective.The clinical manifestations of autosomal dominant IRDs are extremely complex, and there is no appropriate treatment in clinical practice.The latest progresses in pathogenesis, clinical features, treatment strategies and directions of autosomal dominant IRDs globally were reviewed, and the most common genes causing autosomal dominant IRDs were summarized in this article in order to provide a deeper understanding of autosomal dominant IRDs.

Clinical characteristics and gene analysis of a family with autosomal dominant Alport syndrome with the onset of nephrotic syndrome / 中华实用儿科临床杂志

The clinical characteristics, mutation analysis results, and family tree of a patient with autosomal dominant Alport syndrome (ADAS), who had nephrotic syndrome as the first manifestation were examined.The proband was a 11-month-old girl who presented with nephrotic syndromes and gross hematuria.During the treatment course, the patient had steroid resistance and a poor response to Cyclosporine and Cyclophosphamide pulse therapy.Renal biopsy was performed 2 years after disease onset.Under the light microscopy, glomerular segmental mesangio-proliferative lesions were observed.The staining of type Ⅳ collagen showed the loss of the α3 chain in the glomerular basement membrane (GBM) and tubular basement membrane, and α5 chain loss in GBM.Electron microscopy showed uneven thickness of GBM, with obviously delaminated and tearing dense basement membrane (BM) layer, showing a typical lace-like change.The segmental BM was loosened and widened.Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed.A new mutation in the COL4A4 gene was found in the proband, namely c. 1715delG (p.G572Vfs * 81). Her father and grandmother carried the same mutation, but her mother and sister did not have.The clinical manifestation of ADAS is clinically heterogeneous and its incidence may be higher than what we have expected.

Clinical data and mutation analysis of two cases of CHARGE syndrome / 中华内分泌代谢杂志

Objective To analyze the clinical manifestations and possible gene mutation sites of Chinese patients in order to improve the clinician's understanding of CHARGE syndrome. Methods Clinical data were collected and blood samples were obtained from the proband of CHARGE syndrome and their relatives. The peripheral blood DNA was extracted and sequenced by PCR amplification. Mutation sites were verified by Sanger sequencing. Results For the first proband, a heterozygous mutation was detected in the intron 10 of CHD7 gene. His parents and brother did not have mutation. For the second proband, total repeat sequence in exon 7 of CHD7 gene was detected. His father carried the same mutation and his mother did not have mutation. Conclusion For the patients who are diagnosed with CHARGE syndrome based on the clinical manifestations, genetic mutation detection should be proceeded. It is useful for studying possible genetic pathogenesis and enhancing the awareness of clinicians.

Basal cell nevus syndrome: 4 case reports and a literature review / 口腔疾病防治

Objective@#To summarize the incidence, clinical manifestations, diagnosis and treatment of basal cell nevus syndrome and to provide reference for clinical diagnosis and treatment. @*Methods @# Retrospective analysis of 4 cases of basal cell nevus syndrome admitted to the General Hospital of PLA during January 2017 to January 2018 and recent cases reported in the literature.@* Results@#In this study, 1 males and 3 females were included. The patients included a mother and her child. All 4 cases were surgically resected. Pathological reports included all keratocysts of the jaws. There has been no recurrence since follow-up. Through literature summarization and analysis, the clinical manifestations of this syndrome were found to be diverse. Typical clinical manifestations include multiple keratocysts of the jaws, multiple blepharospasms or cancers, deformities of the spine or ribs, increased brachial distance, eye diseases or special face intracranial calcification.@*Conclusion @#Basal cell nevus syndrome is an autosomal dominant genetic disorder. The clinical manifestations are diverse and the diagnosis is often overlooked. The incidence of cysts in the jaws is one of the important clinical manifestations of this syndrome. Early diagnosis and proper treatment improve patient survival and quality of life.

Cleidocranial dysplasia: a case report and gene mutation analysis / 华西口腔医学杂志

Cleidocranial dysplasia is a rare autosomal dominant hereditary disease characterized by abnormal skeletal and dental development. In this work, a case of cleidocranial dysplasia is reported, and a new frameshift mutation is confirmed by gene detection.

Familial misophonia or selective sound sensitivity syndrome: evidence for autosomal dominant inheritance? / Misofonia familiar ou síndrome da sensibilidade seletiva a sons: evidência de herança autossômica dominante?

Abstract Introduction: Misophonia is a recently described, poorly understood and neglected condition. It is characterized by strong negative reactions of hatred, anger or fear when subjects have to face some selective and low level repetitive sounds. The most common ones that trigger such aversive reactions are those elicited by the mouth (chewing gum or food, popping lips) or the nose (breathing, sniffing, and blowing) or by the fingers (typing, kneading paper, clicking pen, drumming on the table). Previous articles have cited that such individuals usually know at least one close relative with similar symptoms, suggesting a possible hereditary component. Objective: We found and described a family with 15 members having misophonia, detailing their common characteristics and the pattern of sounds that trigger such strong discomfort. Methods: All 15 members agreed to give us their epidemiological data, and 12 agreed to answer a specific questionnaire which investigated the symptoms, specific trigger sounds, main feelings evoked and attitudes adopted by each participant. Results: The 15 members belong to three generations of the family. Their age ranged from 9 to 73 years (mean 38.3 years; median 41 years) and 10 were females. Analysis of the 12 questionnaires showed that 10 subjects (83.3%) developed the first symptoms during childhood or adolescence. The mean annoyance score on the Visual Analog Scale from 0 to 10 was 7.3 (median 7.5). Individuals reported hatred/anger, irritability and anxiety in response to sounds, and faced the situation asking to stop the sound, leaving/avoiding the place and even fighting. The self-reported associated symptoms were anxiety (91.3%), tinnitus (50%), obsessive-compulsive disorder (41.6%), depression (33.3%), and hypersensitivity to sounds (25%). Conclusion: The high incidence of misophonia in this particular familial distribution suggests that it might be more common than expected and raises the possibility of having a hereditary etiology.

Resumo Introdução: A misofonia é uma condição recentemente descrita, mal compreendida e negligenciada. É caracterizada por fortes reações negativas de ódio, raiva ou medo quando os indivíduos precisam enfrentar alguns sons repetitivos seletivos e de baixa intensidade. Os mais comuns que desencadeiam tais reações aversivas são aqueles provocados pela boca (mascar goma ou mastigar comida, estalar os lábios) ou nariz (respirando, cheirando e soprando) ou pelos dedos (digitando, amassando papel, clicando a caneta, tamborilando na mesa). Artigos anteriores citam que esses indivíduos geralmente conhecem pelo menos um parente próximo com sintomas semelhantes, sugerindo um possível componente hereditário. Objetivo: Encontramos e descrevemos uma família com 15 membros com misofonia, detalhando suas características comuns e o padrão de sons que desencadeiam um desconforto tão forte. Método: Todos os 15 membros concordaram em nos fornecer seus dados epidemiológicos e 12 concordaram em responder a um questionário específico que investigou os sintomas, sons de gatilho específicos, principais sentimentos evocados e atitudes adotadas por cada participante. Resultados: Os 15 membros pertencem a três gerações da família. A idade variou de 9 a 73 anos (média de 38,3 anos, mediana de 41 anos) e 10 eram mulheres. A análise dos 12 questionários mostrou que 10 indivíduos (83,3%) desenvolveram os primeiros sintomas durante a infância ou a adolescência. A média do escore de irritação na Escala Visual Analógica de 0 a 10 foi de 7,3 (mediana 7,5). Os indivíduos relataram sentimentos de ódio/raiva, irritabilidade e ansiedade em resposta a sons, e enfrentaram a situação pedindo para interromper o som, deixando/evitando o lugar e até mesmo discutindo. Os sintomas associados auto-relatados foram ansiedade (91,3%), zumbido (50%), transtorno obsessivo-compulsivo (41,6%), depressão (33,3%) e hipersensibilidade aos sons (25%). Conclusão: A alta incidência de misofonia nessa distribuição familiar em particular sugere que possa ser mais comum do que o esperado e suscita a possibilidade de haver uma etiologia hereditária.

Estudio dínico y molecular en una familia con displasia ectodermica hipohidrotica autosomica dominante / Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia

La displasia ectodérmica hipohidrótica (DEH) es una entidad infrecuente caracterizada por deficiencia en el desarrollo de estructuras derivadas del ectodermo y es causada por mutaciones en los genes EDA, EDAR o EDARADD, que pueden exhibir hallazgos clínicos similares, debido a una vía de señalización común. Las mutaciones en el gen EDA causan la DEH ligada al X, que es la forma más frecuente. Por su parte, las mutaciones en los genes EDAR y EDARADD causan la DEH con patrón de herencia autosómica dominante y recesiva. Los hallazgos clínicos más resaltantes son hipodoncia, hipotricosis e hipohidrosis, que pueden llevar a episodios de hipertermia. Se presentan los hallazgos clínicos en un niño con DEH con patrón de herencia autosómica dominante, cuyo análisis molecular demostró mutación heterocigótica c.1072C>T (p.Arg358X) en el gen EDAR, y se discuten los diferentes aspectos clínicos encontrados en esta mutación en los casos descritos en la literatura.

Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed.

Genetic localization and clinical classification of congenital fibrosis of the extraocular muscles in 2 Chinese families / 眼科新进展

Objective To determine the pathogenic mutant gene and the classification for 2 Chinese families with congenital fibrosis of the extraocular muscles (CFEOM) by using candidate genes methods.Methyls All members in the 2 Chinese families with CFEOM were collected and underwent for clinical data collection,including medical history,physical examination and 5-8 mL peripheral venous blood for DNA extraction.Exon 2,8,20,21 of KIF21A,exon 1,2,3 of PHOX2A/ARIX,exon 1,2,3,and 4 of TUBB2B and exon 1,2,3,4 of TUBB3 were selected and synthesized by PCR,and the amplified samples were purified for sequences analysis by Chromas2.3 and DNAman7.0 software.Results There were 9 members developed CFEOM in family 1,with the typical CFEOM characteristics.The mutation site was located in KIF21A (exon 21),2860C ＞ T;and 4 patients in family 2 suffered this disease,and the typical CFEOM appearance features was in 3 patients.The mutation site was located in TBUU3 (exon 4),1249 G ＞ A.Conclusion The candidate genes methods can be used to identify the pathogenic genes of pedigrees with inherited diseases effectively.Family 1 belongs to CFEOM 1A type,which is the autosomal dominant inheritance with complete penetrance,and family 2 belongs to CFEOM 3A type,whivh is the autosomal dominant inheritance with incomplete penetrance.

Progress in genetics of autosomal dominant hereditary spastic paraplegia / 上海交通大学学报（医学版）

Hereditary spastic paraplegia (HSP) is a group of significantly clinically and genetically heterogeneous neurodegenerative disorders, which are predominantly characterized by progressive lower limbs weakness and spasticity inducing gait abnormalities or disorders. In practice, based on the modes of inheritance, it can be divided into autosomal dominant, autosomal recessive, X-linked and mitochondrial maternal inheritance. According to whether the clinical manifestations complicated or not, HSP can be divided into pure and complex form. To date, mutations in 78 distinct loci and 59 mutated gene products have been identified or reported in patients with HSP; among them 20 distinct loci and 13 mutated gene products have been found in autosomal dominant spastic paraplegia. This is a review about the genetic characteristics and research progress of autosomal dominant HSP.

Changing spectrum of Zimmerman-Laband syndrome: a six years follow up case report of a family.

The Zimmermann-Laband syndrome (ZLS) is a rare genetic disorder inherited as an autosomal dominant fashion, with clinical characters like, gingival fibromatosis, bulbous soft nose, thick floppy ears, nail dysplasia, joint hyperextensibility, hepatosplenomegaly, skeletal anomalies and occasional mental retardation. Idiopathic gingival enlargement is a hereditary condition; it can be expressed as autosomal dominant inheritance. Here association of Idiopathic gingival enlargement has been reported in a family, with an autosomal dominant inheritance diagnosed to be ZLS. Other clinical features associated are, hypertrichosis, bulbous soft nose, thick floppy ears, nail dysplasia, joint hyper extensibility, bimaxillary protrusion and enlarged palm and fingers with flat feet. The unusual clinical presentations of massive gingival fibromatosis, unusual length of upper limbs and bimaxillary protrusion supported the variable spectrum of phenotype expression of the ZLS. The Biopsy report confirmed the diagnosis of gingival fibromatosis. Gingivectomy was carried out in all four quadrants for exposing the natural teeth and to bring back the original contour of the gingiva. But there was recurrence of the enlargement found to be associated during 6 years follow up.

Informe clínico de dismorfias múltiples con agregación familiar / Clinical report on multiple dysmorphias with familial aggregation

Se comunican las características clínicas de una mujer de 68 años de edad y sus dos hijas (36 y 33 años) que presentaban un conjunto de anomalías de probable origen hereditario. Se les efectuaron interconsultas con varias especialidades: medicina interna, genética, cardiología, radiología, angiología, psiquiatría, dermatología, otorrinolaringología, máxilo-facial, oftalmología y neurología. Los hallazgos comunes a las tres pacientes consistieron en tortuosidad de los vasos retinianos, glaucoma crónico de ángulo abierto, braquidactilias y otros dismorfismos en dedos de manos y pies, hallux valgus, telangiectasias en mejillas y tórax superior, orejas en ®asa», hiperostosis frontal, tórax excavado e insuficiencia mitral. El glaucoma neovascular se presentó en un ojo de cada hija. Este complejo padecimiento clínico, con alteraciones en miembros, faciales, cardiovasculares, oculares y en piel con una posible herencia de tipo autosómico dominante por su presencia en dos generaciones sucesivas, no se corresponde con ningún síndrome de los considerados en este informe

Presentation of the clinical characteristics of a 68-year-old woman and her two daughters, aged 36 and 33, who had a number of abnormalities of probable hereditary origin. Interconsultations were conducted with several specialties: internal medicine, genetics, cardiology, radiology, angiology, psychiatry, dermatology, otorhinolaryngology, maxillofacial, ophthalmology and neurology. The findings common to the three patients were retinal arterial tortuosity, chronic open angle glaucoma, brachydactyly and other dysmorphic disorders of fingers and toes, hallux valgus, telangiectasia in cheeks and upper thorax, protruding ears, frontal hyperostosis, pectus excavatum and mitral insufficiency. Both daughters had neovascular glaucoma in one of their eyes. This complex clinical condition, with disorders involving limbs, face, the cardiovascular system, eyes and skin, and a potential autosomal dominant inheritance in view of its presence in two successive generations, does not correspond to any of the syndromes considered in this report

Camurati-Engelmann Disease.

Camurati-Engelmann disease (CED) is a very rare autosomal dominant genetic disorder that causes characteristic anomalies in the skeleton. It is a connective tissue disorder known for marked variability of its clinical presentation. The authors report CED in a 25-year-old male with atypical involvement of metacarpals (acrosclerosis) and features of neuromuscular disease along with the classical features of the disease.

A Case of Focal Acral Hyperkeratosis

Focal acral hyperkeratosis (FAH) is a rare genodermatosis with an autosomal dominant pattern of inheritance; however, it may also be sporadic. FAH is characterized by late-onset crateriform keratotic papules, some coalescing into plaques, along the borders of the hands and feet. We herein report a case of FAH in a 47-year-old male with a family history of similar lesions in three generations. The histological findings revealed focal areas of orthohyperkeratosis over an area of depressed but otherwise normal epidermis. The dermis showed no specific changes, which distinguished this case from acrokeratoelastoidosis, which shows elastorrhexis of clinically similar lesions.

Autosomal Dominant Centronuclear Myopathy with Unique Clinical Presentations

Centronuclear myopathies are clinically and genetically heterogenous diseases with common histological findings, namely, centrally located nuclei in muscle fibers with a predominance and hypotrophy of type 1 fibers. We describe two cases from one family with autosomal dominant centronuclear myopathy with unusual clinical features that had initially suggested distal myopathy. Clinically, the patients presented with muscle weakness and atrophy localized mainly to the posterior compartment of the distal lower extremities. Magnetic resonance imaging revealed predominant atrophy and fatty changes of bilateral gastrocnemius and soleus muscles. This report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy.

Bilateral Duane's Retraction Syndrome Treated with Bilateral Horizontal Transposition of Vertical Recti

PURPOSE: To report a male infant with bilateral Duane's retraction syndrome treated with bilateral horizontal transpositions of vertical recti to the lateral rectus muscle. METHODS: An 8-month-old boy showed bilateral Duane's retraction syndrome with esotropia of 45PD, severe limitation of abduction (-4 and -3.5 in each eye) and mild globe retraction in both eyes. It was assumed that he inherited the condition from his father through an autosomal dominant pattern. His father showed esotropia of 25PD with -4 limitation of abduction in the left eye and a left head-turn of 10 degrees. He also had +2 globe retraction, +1 upshoot and +2 downshoot in adduction of the left eye. Transposition of two vertical recti to the lateral rectus muscle was performed in both eyes of the boy. RESULTS: Nine months after surgery, the boy had achieved a microesotropia of 6PD in primary gaze with stereopsis of 3000 seconds of arc and considerable improvement in abduction (-2, -1.5 in each eye). The amount of correction of esodeviation was 39PD. This favorable state was maintained at follow-up 3.5 years after surgery. CONCLUSIONS: An 8-month-old boy who had esotropia of 45PD caused by bilateral Duane's retraction syndrome, underwent bilateral horizontal transpositions of vertical recti to the lateral rectus muscle. He achieved a microesotropia of 6PD in primary gaze and considerable improvement of abduction with only mild eyeball retraction.

A Case of Familial Writer's Cramp

Writer's cramp is one of the most frequent type of task-related dystonia. It is primarily defined by the appearance of involuntary muscle contractions soon after one begins to write and often co-exists with postural tremor. The cause of writer's cramp as well as other focal dystonia is still a matter of debate. Although the genetic background of some dys-tonia was well known, there have been few cases of writer's cramp that involve other family members. We experienced one family with writer's cramp and postural tremor. A 42-year-old man noted handwriting difficulty of gradual onset which began with postural tremor at the age of 25. When he wrote certain letters or numbers, he automatically had to press hard or hold the pen tightly, experiencing tremor as well as dystonia. His mother and four siblings also had simi-lar disabilities. All were right-handed, and had a postural tremor, prominent in their right hands. They noted the onset of symptoms between the age of 20 and 40. The symptoms had slowly progressed over a period of years and no patient described a remission of symptoms. Two of them eventually no longer attempted to write due to writer's cramp. Two members could write but barely readable and the other two had minimal distress. Alcohol somewhat relieved the cramp in only one of them. Levodopa was no beneficial to the cramp and baclofen relieved the cramp minimally. We report this rare case with familial writer's cramp and postural tremor that suggests autosomal dominant inheritance.

Study on the clinic, neuro-electrophysiology of Charcot-Marie-Tooth disease type 1A and its gene mutation analysis / 临床神经病学杂志

Objective To study the clinical, neuro-electrophysiology features of Charcot-Marie-Tooth disease type 1A (CMT1A) and its gene mutation analysis.Methods 9 members of the family with CMT1A underwent detailed clinical examinations and gene mutation analysis was carried out in 7 of them. The probands accepted electromyography and nerve, muscle biopsy.Results Five patients of the family were attacked and consistent with autosomal dominant inheritance type. Except one asymptomatic patient, age at onset was in the first or second decade. The clinical features were slowly progressive distal muscle weakness, atrophy and end-brush form sensory decrement, diminished or absent tendon reflexes, foot deformity(pes cavus).The probands showed highly decreased sensory and motor conduction velocities. Gene mutation analysis showed large fragment tandem duplication containing peripheral myelin protein 22(PMP22) gene in all four patients out of the seven family members who attended the gene diagnosis.Conclusion CMT1A is the most common form of CMT. The disease usually begins in childhood or adolescence. Clinical featurs include progressive distal muscle weekness and atrophy, diminished or absent tendon reflexes. The motor nerve conduction velocity is slowed below the limit of 38 m/s. Tandem duplication on chromosome 17p11.2, encompassing the PMP22 gene is the main mutation type of CMT1A.

Study on the clinic,neuro electrophysiology and molecular biology of Machado Joseph disease / 临床神经病学杂志

Objective To study the clinic, neuro electrophysiology and molecular biology of Machado Joseph disease (MJD).Methods Family visiting, physical examination and the blood samples were analysed on molecular biology in 44 members of a family with MJD.The cases of inpatients were examined on cerebrospinal fluid and neuro electrophysiology.Results 10 patients of the family attacked,which were consisted with autosomal dominant inheritance type. Age of the onset was 8~38 years old. The clinical characteristic was progressive severe spinocerebellar of ataxia,faciolingual myokymia,bulging eyes.Change of denervated muscle was revealed by neuro etectrophysiological examination. Light atrophy was observed in cerebellar,brain stem, spinal cord.The genetic defect of MJD was located the long arm of chromosome 14 between D 14 S 280 and D 14 S 81 , their distance was 3.0 cm.All tested patients had their CAG repeated expansion from 72 to 84 in the MJD gene.Conclusion MJD is a neuro degenerative disorder of autosomal dominant inheritance. The disease was clinically characterized by progressive severe spinocerebellar ataxia, no obvious changes of cerebrospinal fluid,neuro electrophysiology, CT and MRI.The genetic defect of MJD was located the long arm of chromosome 14.The number of CAG repeated expansion mutation was associated with the age of the onset.