CAJ | 학술논문

目的：识别先天性房间隔缺损（ASD）相关 GATA6基因新突变。方法：收集110例先天性 ASD 患者和200名健康对照者的临床资料和血标本，使用 DNA 纯化试剂盒提取基因组 DNA。通过聚合酶链反应扩增 GATA6基因的编码外显子和其两侧的部分内含子，应用双脱氧核苷链末端合成终止法进行 DNA 测序。将所测序列与GenBank 数据库中的 GATA6基因序列进行比对，识别 GATA6基因突变。分别借助在线程序 MUSCLE 和 MutationTaster 评估突变氨基酸的保守性和致病性。结果：在1例家族史阴性的先天性 ASD 患者发现了1种新的 GATA6基因杂合错义突变，即p．Q363E突变，突变率约为0．91％。该突变不存在于200名健康对照者，多物种序列比对显示，被改变氨基酸在进化上高度保守，致病性预测表明这种变异为致病性突变。结论：发现 ASD 相关 GATA6基因新突变，有助于揭示 ASD 新的分子机制。
목적：식별선천성방간격결손（ASD）상관 GATA6기인신돌변。방법：수집110례선천성 ASD 환자화200명건강대조자적림상자료화혈표본，사용 DNA 순화시제합제취기인조 DNA。통과취합매련반응확증 GATA6기인적편마외현자화기량측적부분내함자，응용쌍탈양핵감련말단합성종지법진행 DNA 측서。장소측서렬여GenBank 수거고중적 GATA6기인서렬진행비대，식별 GATA6기인돌변。분별차조재선정서 MUSCLE 화 MutationTaster 평고돌변안기산적보수성화치병성。결과：재1례가족사음성적선천성 ASD 환자발현료1충신적 GATA6기인잡합착의돌변，즉p．Q363E돌변，돌변솔약위0．91％。해돌변불존재우200명건강대조자，다물충서렬비대현시，피개변안기산재진화상고도보수，치병성예측표명저충변이위치병성돌변。결론：발현 ASD 상관 GATA6기인신돌변，유조우게시 ASD 신적분자궤제。
Objective:To identify the novel GATA6 mutation associated with congenital atrial septal defect (ASD). Methods:A cohort of 110 unrelated patients with congenital ASD and a total of 200 unrelated healthy individuals as controls were enrolled.Clinical data were collected and peripheral venous blood samples were prepared.Genomic DNA was extracted with DNA extraction kit.The coding exons and their flanking introns of the GATA6 gene were amplified by polymerase chain reaction and the amplicons were sequenced with di-deoxynucleotide chain termination technique.The obtained sequences were aligned with those of GATA6 released from GenBank to identify the sequence variations.The online programs of MUSCL and MutationTaster were used to determine whether the altered amino acid was conserved evolutionarily and whether the mutation was pathogenic,respectively. Results:One novel heterozygous GATA6 mutation, p.Q363E, was identified in an ASD patient, with a mutational prevalence of roughly 0.91 %. This mutation, which altered the amino acid highly conserved evolutionarily,was absent in the 200 control persons and was predicted to be disease-causing. Conclusion:This study associates a novel GATA6 mutation with congenital ASD,helping to unveil new molecular mechanism implicated in the pathogenesis of congenital ASD.