两个遗传性多发性外生性骨疣家系EXT基因的突变分析

Mutation analysis of EXT genes in two pedigrees with hereditary multiple exostoses

目的分析两个遗传性多发性外生性骨疣家系的遗传学致病病因，为家系内相关成员的遗传咨询提供依据。方法应用聚合酶链反应和DNA直接测序技术对两个遗传性多发性外生性骨疣家系中先证者的相关致病基因EXTI和EXT2进行突变分析；进一步对家系其他成员及200名正常对照进行突变点的验证。结果家系1先证者及另外4例患者EXT1基因第1外显子存在C．346_356delinsTAT杂合移码突变，家系2先证者及另外3例患者EXT1基因第10外显子存在C．2009—2012del（TCAA）杂合缺失突变。在家系正常成员和200名正常对照的EXT1基因中未检出上述突变。2个家系均未在EXT2基因中检测到突变。结论在两个遗传性多发性外生性骨疣家系中检出两个EXTI基因的新致病突变，这些新突变的检出为家系遗传咨询提供了依据，并且丰富了EXTI基因的突变谱。

Objective To detect the underlying genetic defect in two Chinese families with hereditary multiple exostoses and provide genetic counseling. Methods Potential mutations in EXT1 and EXT2 genes in the probands were detected by direct sequencing of PCR-amplified exons. Suspected mutations were verified in all available family members and 200 unrelated healthy controls. Results A heterozygous frameshift mutation c. 346_356delinsTAT in exon 1 of EXT1 and a heterozygous deletion mutation c. 2009-2012del （TCAA） in exon 10 of EXT1 were respectively detected in affected members from the two families. The same mutations were not detected in unaffected members and 200 unrelated healthy controls. No mutations in EXT2 were detected in the two families. Conclusions Two novel mutations of EXT1 have been detected in association with hereditary multiple exostoses in two Chinese families. Above results have provided a basis for genetic counseling for the two families and expanded the spectrum of EXT1 mutations.