EXT2基因IVS2+1G>A突变致遗传性多发性外生性骨疣

A mutation IVS2+1G>A in EXT2 gene causes hereditary multiple exostoses

目的 确定一个遗传性外生性骨疣家系的致病基因。方法 应用基因组扫描方法 ,利用 8、11和 19号染色体上的微卫星标记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测序分析寻找突变 ,并行逆转录 - PCR扩增 m RNA加以证实。结果 该家系致病基因被定位在 11号染色体的 EXT2基因区 ,在 EXT2基因中检测到 1个 IVS2 +1G>A(5 36 +1G>A)突变 ,该突变与疾病共分离。逆转录 - PCR证实 ,该突变导致编码区的第 316～ 5 36位共 2 2 1个碱基的缺失 ,使 10 6位密码子至 178位密码子及紧随的两个核苷酸的缺失 ,造成移码 ,形成 12 5个氨基酸的截短蛋白。结论 EXT2基因的 IVS2 +1G>A突变是导致这个家系发生外生性骨疣的原因。

Objective To identify the gene causing hereditary multiple exostoses in a Chinese pedigree. Methods Linkage analysis was carried out in the family using microsatellite markers on chromosome 8,11 and 19 respectively. To detect the mutation, the whole coding sequence and the intron-exon boundaries of the candidate gene were amplified and sequenced. The reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the mutated mRNA. Results The disease-causing gene of the family was linked to the EXT2 locus on chromosome 11. A mutation IVS2+1G>A was detected in EXT2 and resulting in 221 bp deletion from 316 to 536 of coding sequence(CDS), which was co-segregated with the disease phenotype. This change led to deletion from codon 106 to codon 178 and subsequent 2 nucleotides, producing a frameshift and truncated protein of 125 aa. Conclusion The mutation IVS2+ 1G>A is the disease-causing mutation in the Chinese pedigree with hereditary multiple exostoses.