山西汉族遗传性多发性骨软骨瘤家系EXT1及EXT2基因突变研究

Screening for EXT1 and EXT2 gene mutations in a ethnic Han Chinese family from Shanxi with hereditarymultiple exostoses

目的对山西一个汉族遗传性多发性骨软骨瘤家系的EXTl和EXT2基因的全部外显子序列进行分析，以寻找致病突变。方法用PCR扩增先证者EXTl和EXT2基因的全部外显子，将PCR产物送直接测序分析。结果发现EXT1基因2种同义突变（P477P、E587E）、3种内含子突变（C．1537－48A〉G、C．1721＋203A〉G、c．1722－1。3c〉G）。EXT2基因共发现5种内含子突变（C．－29－148A〉T、C．1080－18T〉A、C．1336－93C〉T、C．1526－166C〉T、C．1526－195C〉T）。其中，EXTlP477P、EXTlE587E和EXT2C．1080－18T〉A为多发性骨软骨瘤突变数据库已收录的多态位点，其余7个位点尚未见报道。结论对该家系EXT1、EXT2基因全部外显子的测序分析未发现明确的致病突变，该家系遗传性多发性骨软骨瘤的发生是否由除EXTl、EXT2外的其它EXT相关基因引起尚需进一步的连锁定位分析。

Objective To screen for potential mutations in a ethnic Han Chinese family from Shanxi with hereditary multiple exostoses. Methods Polymerase chain reaction and DNA sequencing were used to screen potential mutations in EXT1 or EXT2 genes. Results For EXT1 gene, two synonymous mutations （P477P and E587E）, three intronie mutations （c. 1537 --48 A〉G, c. 1721 ＋203 A〉G and c. 1722 --103 C〉G） were detected. For EXT2 gene, five intronic mutations （c. --29 --148 A〉T, e. 1080 --18 T〉A, c. 1336 --93 C〉T, c. 1526 --166 C〉T, and c. 1526 --195 C〉T） were identified. Among these, EXT1 P477P, EXT1 E587E and EXT2 c. 1080 --18 T〉A are polymorphisms listed by Multiple Osteochondroma Mutation Database, whilst the other 7 sites have not been reported. Conclusion No mutations have been found among all exons of the EXT1 and EXT2 genes in this family. Linkage analysis is necessary to identify the cause of disease.