1例遗传性多发性骨软骨瘤家系EXT1基因分析

A splicing mutation of EXT1 in a Chinese pedigree with hereditary multiple exostoses

目的遗传性多发性骨软骨瘤(HME)是一种常染色体单基因显性遗传骨发育异常疾病,超过70%为EXT1、EXT2突变所致。该文目的是分析一HME家系(3代24名成员,6名HME患者)临床特征及致病基因与突变;并通过文献复习统计分析中国人种基因突变情况。方法收集、整理、分析该家系临床资料;应用PCR及直接测序进行EXT1基因分析;应用Pubmed及万方数据库检索中国人种HME基因突变文献。结果 (1)该家系起病年龄逐代变早,骨软骨瘤发作部位及数量逐代增多,身体变形逐代严重。(2)患者均发现EXT1基因杂合剪切突变IVS5+1G>A,该突变在中国人中首次发现。(3)至今中国HME家庭(含该家系)基因突变构成比为EXT1为29%(26/90),EXT2为43%(39/90)。结论 (1)该HME家系呈现病情逐代加重情况。(2)该家系由EXT1基因剪切突变IVS5+1G>A导致发病。(3)中国人种EXT1、EXT2突变构成比与西方人不一致。

Objective Hereditary multiple exostoses （HME） is an autosomal dominant monogenic disorder of paraplasia ossium. Mutations in EXT1 and EXT2 have been suggested to be responsible for over 70% of HME cases. This study aimed to analyze the clinical features and pathogenic mutations in a Chinese family with HME （6 patients in 24 members of 3 generations） and to review the relative literature regarding mutations in EXT1 and EXT2 in the Chinese population. Methods Clinical pedigree dada from a Chinese family of HME were collected and analysed. EXT gene mutations in this pedigree assessed by PCR and sequencing. Pubmed and Wanfang （a Chinese database） were searched for the literature related to gene mutations in Chinese HME patients. Results In the pedigree analyzed, the age of onset of HME was becoming younger, the disease was becoming more severe, and the number of osteochondromas was increasing, in successive generations. A splicing mutation IVS5＋ 1 G〉A, first identified in Chinese population, was found in all diseased members of this pedigree. According the currently available literature, EXT1 and EXT2 mutations have been detected in 29% （26/90） and 43% （39/90） Chinese families with HME. Conclusions HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed. A splicing mutation, IVS5＋ 1 G〉 A, of EXT1, first identified in Chinese population, may be responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be different between the Chinese and Western populations.