摘要目的 确定一个遗传性多发性骨软骨瘤(hereditary multiple exostoses,HME)家系的致病基因.方法 应用与EXT1、EXT2紧密连锁的短串联重复序列(short tandem repeat,STR)对该家系进行连锁分析,确定候选基因,然后对候选基因的编码区及外显子与内含子交界处进行PCR-测序法突变分析.结果 该家系致病基因被定位在EXT2基因区,测序发现EXT2基因536G>A无义突变,该突变位于EXT2基因第3外显子,导致编码第180位氨基酸的密码子成为终止密码,突变与疾病共分离,其余外显子未发现突变.另发现1例外显不全.结论 EXT2基因536G>A突变是导致这个家系发生骨软骨瘤的原因.

abstractsObjective To identify the gene causing hereditary multiple exostoses in a Chinese pedigree. Methods Linkage analysis was carried out in the family using microsatellite markers close linkage to the EXT1 and EXT2 genes to define the candidate gene. Then the whole coding sequence and the intronexon boundaries of the candidate gene were amplified and sequenced. Results The disease-causing gene of the family was linked to the EXT2 gene. A nonsense mutation of 536G>A in exon3 of the EXT2 gene was detected, which wasco-segregated with the disease phenotype. The mutation resulted in a stop codon in codon 180. A nonpenetrant case was found in the family. Conclusion The mutation 536G>A in the EXT2 gene is the disease-causing mutation in the pedigree with hereditary multiple exostoses.