Dysferlinopathy患者临床表现与基因突变分析  

Analysis of clinical features and gene mutations in Chinese patients with dysferlinopathy

作　　者：张莹[1] 李懋[1] 张小兰[1] 陈朝晖[1] 凌丽[1] 蒲传强[1] 黄旭升[1] 

机构地区：[1]解放军总医院神经内科,北京100853

出　　处：《北京医学》2015年第5期415-418,共4页Beijing Medical Journal

摘　　要：目的探讨dysferlinopathy患者基因突变与临床表现间的关系。方法应用基因芯片捕获第二代测序技术对25例临床诊断为肌营养不良患者进行基因检测,用Sanger法进行家系验证。通过肌肉活检酶组织化学及免疫组织化学染色方法对部分患者行病理学检查。结果 10例患者存在19个不同位点的DYSF基因突变,其中10个为新位点,错义突变占53%。除1例患者为携带者外,9例诊断为dysferlinopathy,包括4例肢带型肌营养不良2B型、4例Miyoshi远端型肌营养不良、1例小腿前部无力的远端前群肌病,其中8例为复合杂合突变。结论通过本研究,丰富了中国人群中DYSF突变的基因型,进一步加深了对dysferlinopathy临床和遗传高度异质性的认识。Objective To study the clinical features and dysferlin gene mutations. Methods Twenty-five unrelated Chinese patients with suspicious progressive muscular dystrophy were clinically investigated. Gene-capture and nextgeneration sequencing was used to detect dysferlin gene mutations. Sanger sequencing was used to confirm the identifica- tion of single-nucleotide variation mutations in the families of the patients. Results Nineteen mutations were identified in 10 patients including 10 novel mutations. Nine were missense mutation that accounted for the most （53%）. Nine pa- tients were genetically diagnosed with dysferlinopathy, including 4 patients with limb girdle muscular dystrophy type 2B （LGMD2B）, 4 with Miyoshi myopathy dystrophy 1 （MMD1） and 1 with distal anterior compartment myopathy （DACM）. Compound heterozygous mutation was detected in 8 patients. Conclusion The study further enriches the genotype of dysferlin gene and underlines the clinical and genetic heterogeneity in Chinese patients affected with dysferlinopathy.

关 键 词：DYSFERLINOPATHY DYSF基因 第二代测序 复合杂合突变 

分 类 号：R746[医药卫生—神经病学与精神病学]