[中国西南地区170例杜氏/贝氏肌营养不良患者的基因突变谱分析]

[Gene Mutation Spectrum Analysis of 170 Patients with Duchenne/Bayesian Muscular Dystrophy in Southwest of China].

作者信息

Wang Jun, Peng Wu, Hu Xue-jiao, Shang Meng-qiao, Zhou Juan, Zhou Yi, Ye Yuan-xin, Song Xing-bo, Lu Xiao-jun, Ying Bin-wu

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Mar;47(2):232-7.

PMID:27263301

Abstract

OBJECTIVE

To determine gene variations and genotype-phenotype correlations in Duchenne/Bayesian muscular mystrophy (DMD/BMD) patients, and the association between dystrophin gene polymorphisms and clinical phenotype.

METHODS

Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect dystrophin gene variations in 170 patients. Sanger sequencing was performed in 3 cases with decreased peaks in MLPA results.

RESULTS

The MLPA detected 72.94% mutations in dystrophin gene, including 62.35% (106/170) deletions, 8.82% (15/170) duplications, and 1.76% (3/170) point mutations. 64 different types of mutations were found. 75.47% of deletions occurred in the range from exon 44 to 55. Most 5' breakpoints of exonic variations were located in 2 hotspots (major hotspot: intron 43-55; minor hotspot: intron 1-20), which is different from findings of other studies. Genotype-phenotype analysis showed that the severity of DMD/BMD was associated with frame shift mutation (r = 0.640, P < 0.001) but not with deletions or duplications.

CONCLUSION

Deletions and duplications of exon compose the main type of dystrophin gene mutations. DMD/BMD is associated with frame shift mutation.

摘要

目的

确定杜兴氏/贝氏肌营养不良症（DMD/BMD）患者的基因变异及基因型-表型相关性，以及肌营养不良蛋白基因多态性与临床表型之间的关联。

方法

采用多重连接依赖探针扩增技术（MLPA）检测170例患者的肌营养不良蛋白基因变异。对MLPA结果中峰值降低的3例患者进行桑格测序。

结果

MLPA检测到肌营养不良蛋白基因72.94%的突变，其中包括62.35%（106/170）的缺失、8.82%（15/170）的重复和1.76%（3/170）的点突变。共发现64种不同类型的突变。75.47%的缺失发生在外显子44至55范围内。外显子变异的大多数5'断点位于2个热点区域（主要热点：内含子43 - 55；次要热点：内含子1 - 20），这与其他研究结果不同。基因型-表型分析表明，DMD/BMD的严重程度与移码突变相关（r = 0.640，P < 0.001），但与缺失或重复无关。