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目的对一例层黏连蛋白α2缺失型先天性肌营养不良(MDC1A)患儿LAMA2基因突变(c.7147C>T/p.Arg2383X、c.6513_6515delTGT/p.2172delVal)进行报道和分析。方法提取一例MDC1A患儿与其父母的外周血DNA,PCR扩增LAMA2基因的全部65个外显子,以琼脂糖凝胶电泳鉴定PCR产物,PCR产物纯化后进行直接基因测序。结果检测到先证者LAMA2基因的多种突变,其中c.7147 C>T(杂合)为无义突变(p.Arg2383X);另一个突变c.6513_6515delTGT(杂合)引起编码产物缺失单个氨基酸残基(p.2172delVal),其余突变均发生于多态性位点或内含子区,仅有较小可能影响LAMA2基因的功能。先证者母亲被检出携带了c.6513_6515delTGT杂合突变;父亲被检出携带了c.7147C>T杂合突变。结论先证者一个LAMA2等位基因发生c.7147 C>T杂合突变,另一个等位基因发生c.6513_6515delTGT杂合突变,两个突变位点均位于编码蛋白laminin-2的G区域,突变导致G区域功能丧失,引起MDC1A的表现型。
Objective To report and analyze the mutation of LAMA2 gene (c.7147C> T / p.Arg2383X, c.6513_6515delTGT / p.2172delVal) in a patient with laminin α2 deletion congenital muscular dystrophy (MDC1A). Methods A total of 65 exons of LAMA2 gene were amplified from peripheral blood of a MDC1A patient and their parents. PCR products were identified by agarose gel electrophoresis. The PCR products were purified and sequenced directly. Results Multiple mutations of proband LAMA2 gene were detected, of which c.7147 C> T (heterozygous) was a nonsense mutation (p.Arg2383X) and the other mutation c.6513_6515delTGT (heterozygous) resulted in the deletion of a single amino acid Residues (p.2172delVal), the rest of the mutations occurred in polymorphic sites or intron regions, with only minor possible effects on LAMA2 gene function. The proband’s mother was found to carry a c.6513_6515delTGT heterozygous mutation; his father was found to carry a c.7147C> T heterozygous mutation. CONCLUSIONS: One LAMA2 allele of the proband was c.7147 C> T heterozygous mutation and the other allele was c.6513_6515delTGT heterozygous mutation, both of which were located in the G region of the protein laminin-2, and the mutation Resulting in loss of function in the G region, causing the phenotype of MDC1A.