高通量全外显子测序诊断2A型肢带型肌营养不良1例

Diagnosis of a case with type 2A of limb-girdle muscular dystrophy by high-throughput sequencing

目的对1例患有肌营养不良的中国籍汉族男孩进行临床分子诊断。方法运用高通量测序技术对1例已排除杜氏/贝氏进行性肌营养不良(DMD/BMD)的患儿进行外周血有核细胞基因全外显子组测序(WES),并使用Sanger测序对WES发现的基因相关突变进行验证。结果 WES发现钙蛋白酶3基因(CAPN3)存在复合杂合突变,其中3号外显子区域发现1个杂合的无义突变c.439C>T,p.Arg147*,而13号外显子存在1个杂合的错义突变c.1621C>T,p.Arg541Trp。结论借助高通量DNA测序技术,该患者最终被诊断为2A型肢带型肌营养不良(LGMD)。

Objective To perform the clinical molecular diagnosis in a Chinese Han boy with musculardystrophy. Methods This boy had been diagnosed to exclude Duchenne and Becker muscular dystrophy(DMD/BMD). The whole exome sequencing(WES) was performed for his peripheral blood genomic DNA,and therelevant mutations identified by WES were verified by Sanger sequencing. Results WES results revealed thatcalpin 3 gene(CAPN3) existed 2 compound heterozygous mutations. One is a heterozygous nonsense mutationc.439C>T,p.Arg147* in exon 3,while exon 13 had another heterozygous missense mutation c.1621C>T,p. Arg541Trp. Conclusions By high-throughput sequencing,the patient is eventually diagnosed as type 2A oflimb-girdle muscular dystrophy(LGMD).