Nonaka肌病的GNE基因突变研究

Novel mutations in GNE gene in Chinese patients with Nonaka myopathy

目的报告2例Nonaka肌病的GNE基因突变特点。方法对2例经临床和病理检查证实的Nonaka 肌病,用PCR和DNA测序方法检测GNE基因编码区外显子及其侧翼序列,对例1家系中3代共7人也作该基因的突变检查。结果例1在GNE基因外显子8出现1 525C→T纯合突变;例2在外显子2出现527A→T杂合突变和外显子9出现1714G→C杂合突变,上述突变分别造成GNE出现H509Y的纯合突变以及D176V和V572L的复合杂合突变。例1的家系中患者的父母分别为H509Y的杂合突变。结论我们这2例Nonaka肌病患者的发病均是由GNE 基因突变所致,其中H509Y突变为新发现的突变类型。同时也证实我国Nonaka肌病也存在日本患者GNE的热点突变。

Objectives To search for mutations in GNE gene in Chinese patients with Nonaka myopathy. Methods Two patients from two unrelated families with typical clinical and pathological features of Nonaka myopathy were studied. All of the 11 coding exons and their flanking intron sequences of GNE gene were amplified by PCR and sequenced. Additionally,seven members of three consecutive generations in case 1 family were also exam ined for the GNE gene mutations. Results The two patients were identified to have different GNE gent muta tions：case 1 having a homozygous point mutation of 1525C→T that resulted in homozygous amino acid substitutions of H509Y ;case 2 carrying compound heterozygous point mutations of 527A→T and 1714G→C which caused heterozygous amino acid changes of D176V and V572I.,respectively. H509Y was a novel mutation not reported previously. In the family of case 1 ,his father,mother,sister and son were disease carriers and harbored the same heterozygous mutation with the proband. Conclusions Homozygous missense and compound heterozygous missense mutations in GNE gene are found in Chinese patients with Nonaka myopathy. H509Y might be a novel mutation.