伴镶边空泡远端肌病患者GNE基因突变分析

GNE gene mutation analysis in 5 patients with distal myopathy with rimmed vacuoles

目的探讨5例伴镶边空泡远端肌病(DMRV)患者GNE基因突变类型。方法对5例患者行肌活检,所有患者及例5的父母、妹妹、女儿行GNE基因编码区外显子及其侧翼序列聚合酶链反应扩增,纯化后产物经测序比对分析基因突变点,应用SnaPshotTM技术在100名健康对照者中进行新发突变位点检测。结果 5例患者均携带GNE基因突变,例1-4为复合杂合子,例5为纯合子。共检测到已知突变6个,1个无义突变(p.R8X),5个错义突变(p.D176V、p.I298T、p.A591T、P.A631V、p.V696M),发现新发错意突变1个(c.317T>C,p.I106T),例5父母、妹妹及女儿均为P.A631V健康携带者。结论本研究为p.R8X、p.I298T、p.A591T、p.V696M突变首次在中国人群中的报道,且p.I106T为GNE基因新发突变,这些发现进一步扩展了中国人群GNE基因突变谱。

Objective To investigate GNE gene mutations in 5 Chinese patients with distal myopathy with rimmed vacuoles（DMRV）.Methods Five patients with typical clinical and pathological features of DMRV were studied.All the 11 coding exons and the flanking intron sequences of GNE gene were amplified by PCR and sequenced.Four family members of case 5 were also examined for GNE gene mutations.Results All the patients were identified to have different GNE gene mutations：Cases 1-4 had complex heterozygous mutations and case 5 had homozygous mutation.Six reported mutations had been indentified,including 1 nonsense mutation（p.R8X） and 5 missense mutations（p.D176V,p.I298T,p.A591T,P.A631V,and p.V696M）.A novel mutation（c.317TC,p.I106T） was identified in case 2.Conclusions This is the first report of p.R8X,p.I298T,p.A591T and p.V696M mutations in GNE gene in Chinese population,and a novel mutation p.I106T was identified.These findings further expand the clinical and genetic spectrum of DMRV in China.