一个2D型肢带肌营养不良家系的基因变异分析

Variant analysis for a pedigree affected with limb-girdle muscular dystrophy type 2D

目的 运用全外显子测序技术对1个2D型肢带肌营养不良家系的SGCA基因进行变异分析,明确患儿的病因。 方法 应用多重连接探针扩增技术对该家系的先证者进行DMD基因大片段缺失/重复筛查,用FastTarget?富集二代测序+Sanger测序验证技术对DMD基因变异检测。在完成先证者DMD排查后,用全外显子测序技术对先证者及其父母进行检测,用Sanger测序技术进行致病基因变异位点验证。 结果 先证者DMD基因变异及筛查结果均为阴性。全外显子测序发现其SGCA基因存在c.409G>A(p.Glu137Lys)和c.409G>C(p.Glu137Gln)复合杂合变异,先证者父亲为SGCA基因c.409G>C(p.Glu137Gln)变异携带者,先证者母亲为SGCA基因c.409G>A(p.Glu137Lys)变异携带者,胎儿未检测到此位点变异。 结论 c.409G>A(p.Glu137Lys)和c.409G>C(p.Glu137Gln)复合杂合变异为患儿的致病原因。

Objective To analyze variant of SGCA gene in a Chinese pedigree affected with limb-girdle muscular dystrophy type 2D with whole exome sequencing (WGS).Methods Multiplex ligation-dependent probe amplification (MLPA) was employed to detect large fragment deletion or duplication of the DMD gene. FastTarget? next generation sequencing was used to detect variants of the DMD gene, and the result was verified by Sanger sequencing. After excluding the diagnosis of DMD for the proband, WGS was applied to test the proband and his parents. Suspected pathogenic variants were validated by Sanger sequencing.Results No variant, deletion or duplication of the DMD gene was detected. Whole exome sequencing showed that the proband has carried compound heterozygous missense variants c. 409G>A (p.Glu137Lys) and c. 409G>C (p.Glu137Gln) in exon 5 of the SGCA gene, which were respectively inherited from his mother and father. Neither variant was found in DNA derived from the cord blood sample.Conclusion The c. 409G>A (p.Glu137Lys) and c. 409G>C(p.Glu137Gln) compound heterozygous missense variants probably underlie the disease in the proband. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.