Thiel-Behnke Corneal Dystrophy in a Young Man in Denmark—A Case Report

Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.

乌帕替尼治疗20甲营养不良一例

20甲营养不良(twenty-nail dystrophy,TND)是一种病因不明的甲损害,累及所有指/趾甲,可能由遗传因素及免疫系统异常而诱发。本病目前尚缺乏标准的治疗方案,传统治疗往往起效慢,不良反应明显。本文报道JAK-STAT抑制剂乌帕替尼治疗TND有效一例,患者口服乌帕替尼片15 mg/d,6个月后甲全部新生,减量至15 mg/2d;治疗8个月后,所有甲基本恢复正常。

优化多重PCR检测Duchenne muscular dystrophy基因外显

目的:介绍一种快速简便地优化多重PCR检测DMD基因外显子缺失的方法及详细步骤.方法:采2ml外周血,用0.2%氯化钠处理收集白细胞,再用基因组DNA提取试剂盒抽提基因组DNA,用优化的多重PCR法直接检测DMD基因外显子的缺失.结果:用该方法检测DMD基因外显子缺失结果准确清晰.结论:用优化的多重PCR技术可以直接检测DMD基因外显子缺失,跟通常使用的9对引物一步法相比,具有经济、快速、简便等特点.

深板层角膜移植与穿透性角膜移植治疗基质角膜营养不良预后的比较

背景:基质角膜营养不良的传统手术治疗方式为穿透性角膜移植,近年来越来越多的医生开始考虑使用深板层角膜移植治疗基质角膜营养不良。目前国内对比穿透性角膜移植和深板层角膜移植治疗基质角膜营养不良的研究少有报道。目的:比较深板层角膜移植和穿透性角膜移植治疗基质角膜营养不良的疗效。方法:选择2000年1月至2018年1月北部战区总医院收治的基质角膜营养不良患者57例(57眼),男18例,女39例,平均年龄(52.9±20.0)岁,按照手术治疗方式分为深板层角膜移植组(n=21)、穿性角膜移植组(n=36),术后随访观察最佳矫正视力、角膜内皮细胞密度、角膜植片透明度、术中及术后并发症、原病复发情况。结果与结论:①两组患者术后1,3,6,12个月的视力均高于术前(P<0.05),两组间术后不同时间点的视力比较差异无显著性意义(P>0.05);随着术后时间的延长,两组患者角膜内皮细胞密度逐渐降低,穿透性角膜移植组患者术后6,12个月的角膜内皮细胞密度年丢失率均高于深板层角膜移植组(P<0.05);两组患者术后12个月的角膜植片透明率比较差异无显著性意义(P>0.05);②深板层角膜移植组有6例出现并发症,穿透性角膜移植组有14例出现并发症,57例患者术后12个月内均无复发,两组患者术后5年的复发率比较差异无显著性意义(P>0.05),穿透性角膜移植组和深板层角膜移植组术后5年的移植物存活率分别为83%和86%,组间比较差异无显著性意义(P>0.05);③结果表明,基质角膜营养不良的治疗可考虑使用深板层角膜移植替代一部分穿透性角膜移植。

Cardiac involvement in Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophy(DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation,not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction,heart block or malignant arrhythmias. Not only DMD/BMD patients,but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent,due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects,arrhythmias(supraventricular or ventricular),hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction,independently of age of onset or mutation groups. Cardiovascular magnetic resonance(CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies' patients and carriers that can be observed even if overt muscular disease is absent. Recently,new CMR techniques,such as postcontrast myocardial T1 mapping,have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.

TGFBI gene mutation analysis in a Chinese pedigree of Avellino corneal dystrophy

AIM: To analyze phenotype and genotype of a Chinese pedigree with Avellino corneal dystrophy (ACD). METHODS: Complete ophthalmic EX aminations were performed on all the family members. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: A single heterozygous G>A(R124H) point mutation was identified in exon 4 of TGFBI in three affected members and two unaffected children who were offsprings of the affected members, but not in the other family members. CONCLUSION: Mutation R124H in TGFBI was identified in this pedigree and appeared to be the disease causing mutation. Atypical phenotype and low penetrance was observed in this pedigree..

Stem cell transplantation for treating Duchenne muscular dystrophy A Web of Science-based literature analysis

OBJECTIVE： To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; （b） original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） publication between 2002 and 2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） corrected papers. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） distribution according to subject areas; （3） distribution according to journals; （4） distribution according to country; （5） distribution according to institution; （6） distribution according to institution in China; （7） distribution according to institution that cooperated with Chinese institutions; （8） top-cited articles from 2002 to 2006; （9） top-cited articles from 2007 to 2011. RESULTS： A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION： The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.

Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.

Chinese family with atypical granular corneal dystrophy type I caused by the typical R555W mutation in TGFBI

·AIM: To investigate the clinical features and genetic defects in four generations of a Chinese family affected with atypical granular corneal dystrophy type I (GCD type I). · METHODS: Family history and clinical data were recorded. Genomic DNA samples were obtained from peripheral blood leukocytes of all participated. Exons of the transforming growth factor-β-induced (TGFBI) gene were directly sequenced after being amplified by polymerase chain reaction (PCR), and multi-point linkage analysis using microsatellite makers flanking the gene was applied to identify the disease-causing mutation. · RESULTS: Clinical features were quite variable in patients, some patients only had opacities in the epithelium, and others revealed multiple bilateral circular, discrete, crumb -like opacities mainly in the epithelium, with several in different depths of corneal stroma, and the performance was different bilaterally, even in the same patient. Directly nucleotide sequencing revealed a heterozygous p.R555W mutation in the coding sequence of the TGFBI gene in all affected individuals of the family, but was not found in all unaffected. The maximum logarithm of odds (LOD) score obtained by multi -point analysis was detected at marker locus D5S393 (LOD = 2.740; α=1.000). ·CONCLUSION: Our case presented with clinical futures and the pathogenic mutations in TGFBI gene, the phenotype of the pedigree was quite different from typical GCD type I, so we suggested that this phenotype was a variant of GCD type I. These findings expand the knowledge about GCD type I, and demonstrate that molecular genetic analysis is important to make an accurate diagnosis of patients with variable corneal dystrophies in clinic.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells （6 × 106） were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin （mTOR）, eIF-4E binding protein 1 and $6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the re- generation and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Congenital and childhood myotonic dystrophy:Current aspects of disease and future directions

Myotonic dystrophy type 1(DM1) is multisystem disease arising from mutant CTG expansion in the nontranslating region of the dystrophia myotonica protein kinase gene. While DM1 is the most common adult muscular dystrophy, with a worldwide prevalence of one in eight thousand, age of onset varies from before birth to adulthood. There is a broad spectrum of clinical severity, ranging from mild to severe, which correlates with number of DNA repeats. Importantly, the early clinical manifestations and management in congenital and childhood DM1 differ from classic adult DM1. In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are often under recognised yet a significant morbidity. No effective disease modifying treatment is currently available and neonates and children with DM1 may experience severe physical and intellectual disability, which may be life limiting in the most severe forms. Management is currently supportive, incorporating regular surveillance and treatment of manifestations. Novel therapies, which target the gene and the pathogenic mechanism of abnormal splicing are emerging. Genetic counselling is critical in this autosomal dominant genetic disease with variable penetrance and potential maternal anticipation, as is assisting with family planning and undertaking cascade testing to instigate health surveillance in affected family members. This review incorporates discussion of the clinical manifestations and management of congenital and childhood DM1, with a particular focus on hypersomnolence and sleep disorders. In addition, the molecular genetics, mechanisms of disease pathogenesis and development of novel treatment strategies in DM1 will be summarised.

Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bücklers corneal dystrophy

AIM: To analyze mutations in transforming growth factor beta-induced (TGFBI) gene in a Chinese pedigree with Reis-Bücklers corneal dystrophy (RBCD,also known as GCD3).METHODS: In a five-generation Chinese family,eight members were identified with RBCD and the rest were unaffected.All members of the family underwent complete ophthalmologic examinations.Exons of TGFBI were amplified by polymerase chain reaction,sequenced,and compared with a reference database.RESULTS: A single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all the affected members of the pedigree,but not in the unaffected members.CONCLUSION: R124C which was a known mutation for lattice corneal dystrophy type I,segregated with the RBCD in this pedigree.This elucidated the correlation between genotype and phenotype in a Chinese family of RBCD.

T2 Mapping and Fat Quantification of Thigh Muscles in Children with Duchenne Muscular Dystrophy

Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.

Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

Cardiomyopathy in becker muscular dystrophy:Overview

Becker muscular dystrophy(BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

Recurrent hypotension induced by sacubitril/valsartan in cardiomyopathy secondary to Duchenne muscular dystrophy: A case report

BACKGROUND Duchenne muscular dystrophy(DMD),which is caused by a mutation/deletion in the dystrophin gene on the X-chromosome,is the most common type of neuromuscular disorder in pediatrics.Skeletal muscle weakness progressively develops in DMD patients and usually leads to respiratory failure in the early adolescent years.Cardiac muscle is frequently affected in DMD patients,which leads to a high burden of cardiomyopathy and heart failure.In the era of improved respiratory care,cardiac deaths are becoming the major cause of mortality in DMD patients.CASE SUMMARY We report the case of a 15-year-old boy who presented to the hospital due to recurrent orthopnea for 6 mo and palpitations for 4 mo.He was diagnosed with progressive muscular dystrophy at the age of 3 years and was confined to a wheelchair at 12 years.He was prescribed diuretics and digoxin at the outpatient clinic;however,his symptoms did not resolve.Sacubitril/valsartan was added 1 mo prior to presentation,but he experienced recurrent episodes of palpitations.The electrocardiogram showed atrial tachycardia with a heart rate of 201 bpm,and he was then hospitalized.Hypotension was found following the administration of sacubitril/valsartan tablets;he could not tolerate even a small dose,always developing tachyarrhythmia.His symptoms were relieved after discontinuing sacubitril/valsartan,and his heart rate was controlled by a small dose of metoprolol tartrate and digoxin.Atrial tachycardia spontaneously converted in this patient,and his symptoms attenuated in the following 6 mo,without palpitation episodes.CONCLUSION Blood pressure should be closely monitored in DMD patients with advanced heart failure when taking sacubitril/valsartan.

Novel CYP4V2 mutations associated with Bietti crystalline corneoretinal dystrophy in Chinese patients

AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.

Long term follow-up of a family with GUCY2D dominant cone dystrophy

AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms(ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family(father and son) were identified to have the heterozygous R838 C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13 y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectraldomain optical coherence tomography(SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer.CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.

Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy

Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy （PMD）. Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy （DMD）, Becker muscular dystrophy （BMD） , congenital muscular dystrophy （CMD） by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.

Limb-girdle muscular dystrophy subtypes First-reported cohort from northeastern China

The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy subtypes in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases （17%）, and dysferlin deficiency in 10 cases （15%）. Two biopsies revealed α-sarcoglycan deficiency （3%）, and two others revealed a lack of caveolin-3 （3%）. A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients （62%）. The ap-pearances of calpain 3- and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biop-sies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy sub-types in the Han Chinese population is similar to that reported in the West. The less necrotic, re-generating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing.