2例肢带型肌营养不良患者的临床、病理学、基因学研究
| 作者: |
1,2杨百元,
3何度,
4杨兴隆,
1徐严明
1 四川大学华西医院神经内科，成都 610041 2 成都市第七人民医院神经内科，成都 610041 3 四川大学华西医院病理科，成都 610041 4 昆明医科大学第一附属医院老年神经内科，昆明 650032 |
| 通讯: |
徐严明
Email: neuroxym999@163.com |
| DOI: | 10.3978/j.issn.2095-6959. 2018.12.035 |
| 基金: | 四川省科技厅应用基础研究(2014JY0247)；云南省卫生单位内设研究机构科研项目(2018NS0102)；昆明医 科大学第一附属医院博士基金(2017BS005)。 |
摘要
对2例肢带型肌营养不良(limb-girdle muscular dystrophy，LGMD)患者的临床特点进行分析，并进行相应的肌肉病理学检查，最后通过全外显子测序确定患者的致病基因。病例1进行了肌肉活检，结果支持Dysferlin病；并在其DYSF基因第50号外显子区域发现了c.5639G>A(p.G1880D)， c.5246G>C (p.R1749P) 2个杂合突变，进一步的验证发现2个突变分别来自于患者的母亲和父亲。在病例2的CAPN3基因上发现了2009C>A(p.A670E)纯合突变，进一步验证发现病例2的父母均携带该杂合突变。病例1诊断为LGMD2B，而病例2诊断为LGMD2A。对于LGMD患者，综合临床、病理学方法以及基因学方法能对疾病做出较为明确的诊断。
关键词：
肢带型肌营养不良；全外显子测序；肌肉活检
Clinical, pathological and genetic studies of 2 patients with limb-girdle muscular dystrophy
CorrespondingAuthor: XU Yanming Email: neuroxym999@163.com
DOI: 10.3978/j.issn.2095-6959. 2018.12.035
Foundation: This work was supported by the Sichuan Provincial Science and Technology Department Applied Basic Research Program (2014JY0247), Yunnan Province Medical Health Research Institute Project (2018NS0102) and the First Affiliated Hospital of Kunming Medical University Doctoral Research Fund Project (2017BS005)
Abstract
The clinical features of 2 patients with limb-girdle muscular dystrophy (LGMD) were analyzed, and the corresponding muscle pathological examination was performed. Finally, the pathogenic genes were identified by whole exome sequencing. Patient 1 accepted muscle biopsy that supported Dysferlin’s disease. A composite heterozygous mutation of c.5639G>A (p.G1880D) and c.5246G>C (p.R1749P) was found in exon 50 of the DYSF gene in patient 1; further validation found that the two mutations were from the patient’s mother and father, respectively. A homozygous mutation of 2009C>A (p.A670E) in CAPN3 gene was found in patient 2, and it was further verified that the heterozygous mutation was carried by the parents of patient 2. The patient 1 was diagnosis as limb-type muscular dystrophy 2B, while the patient 2 was limb-type muscular dystrophy 2A. Comprehensive clinical, pathological, and genetic methods for LGMD patients can provide a more definitive diagnosis of the disease.
Keywords：
limb-type muscular dystrophy; whole exon sequencing; muscle biopsy