CAJ | 학술논문

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EXT1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EXT1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EXT1基因的突变谱.
목적 분석량개유전성다발성외생성골우가계적유전학치병병인,위가계내상관성원적유전자순제공의거.방법 응용취합매련반응화DNA직접측서기술대량개유전성다발성외생성골우가계중선증자적상관치병기인EXT1화EXT2진행돌변분석;진일보대가계기타성원급200명정상대조진행돌변점적험증.결과 가계1선증자급령외4례환자EXT1기인제1외현자존재c.346_356delinsTAT잡합이마돌변,가계2선증자급령외3례환자EXT1기인제10외현자존재c.2009_2012del (TCAA)잡합결실돌변.재가계정상성원화200명정상대조적EXT1기인중미검출상술돌변.2개가계균미재EXT2기인중검측도돌변.결론 재량개유전성다발성외생성골우가계중검출량개EXT1기인적신치병돌변,저사신돌변적검출위가계유전자순제공료의거,병차봉부료EXT1기인적돌변보.
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.