CAJ | 학술논문

目的：应用基因测序的方法，对一个常染色体显性遗传的角膜营养不良家系进行基因筛查，确定该家系的基因缺陷。方法收集一个中国人Reis-Bücklers地图状角膜营养不良家系，共4代30人，其中患者12人。对所有家系患病成员及正常同胞进行详细的临床检查及TGFBI基因编码序列分析，包括TGFBI基因的全部17个外显子，5＇及3＇端与外显子拼接的内含子序列。结果对TGFBI基因直接测序显示家系中所有患者在TGFBI基因的第4外显子存在杂合性突变，mRNA第371位碱基出现G→T的杂合性碱基改变，导致了野生型基因编码的Arg被Leu替代，使第124编码子发生了R124L的突变，并且该突变与疾病表型共分离。结论经序列分析确定该家系角膜营养不良患者均存在TGFBI基因第4外显子的R124L突变。
목적：응용기인측서적방법，대일개상염색체현성유전적각막영양불량가계진행기인사사，학정해가계적기인결함。방법수집일개중국인Reis-Bücklers지도상각막영양불량가계，공4대30인，기중환자12인。대소유가계환병성원급정상동포진행상세적림상검사급TGFBI기인편마서렬분석，포괄TGFBI기인적전부17개외현자，5＇급3＇단여외현자병접적내함자서렬。결과대TGFBI기인직접측서현시가계중소유환자재TGFBI기인적제4외현자존재잡합성돌변，mRNA제371위감기출현G→T적잡합성감기개변，도치료야생형기인편마적Arg피Leu체대，사제124편마자발생료R124L적돌변，병차해돌변여질병표형공분리。결론경서렬분석학정해가계각막영양불량환자균존재TGFBI기인제4외현자적R124L돌변。
Objective To identify the gene mutation in a Chinese family with Reis-Bücklers corneal dystro-phy by molecular genetic study. Methods Both affected and unaffected members in this family were examined and extracted the genome-DNA from the samples. The exons of TGFBI genes were sequenced directly. Results The clini-cal diagnosis was Reis-Bücklers corneal dystrophy. The mode of inheritance of corneal dystrophy in this family was i-dentified as autosomal dominant inheritance. Direct sequencing of all affected members revealed a G-to-T transition at codon 124,producing R124L mutation in exon 4 of TGFBI gene.No mutation of this type was identified in all unaf-fected member of this family. Conclusions Reis-Bücklers corneal dystrophy in this family is caused by R124L muta-tion of the TGFBI gene.