CAJ | 학술논문

目的对1例临床怀疑且经尿筛查诊断为琥珀酸半醛脱氢酶缺陷病的患儿及家系进行ALDH5A1基因突变分析,以进一步明确诊断和辅助遗传咨询.方法应用聚合酶链反应及DNA直接测序技术对1例琥珀酸半醛脱氢酶缺陷病患儿及其父母的ALDH5A1基因进行突变位点检测,同时检测100名健康对照者的ALDH5A1基因以排除多态性变异.结果患儿携带有ALDH5A1基因编码区序列第3外显子c.527G＞A(p.Gly176Glu)和第4外显子c.691G＞A(p.Glu231Lys)两种杂合突变,其母亲为c.527G＞A杂合突变携带者,父亲为c.691G＞A杂合突变携带者.另外患儿还存在两种已报道的核酸多态性改变:c.545C＞T杂合突变和c.538C＞T纯合突变.患儿的c.545C＞T突变来源于父亲,c.538C＞T突变分别来源于父母.100名健康对照者中未检测到c.527G＞A和c.691G＞A突变.结论 c.527G＞A(p.Gly176Glu)和c.691G＞A(p.Glu231 Lys)错义突变可能是该患儿的致病突变.
목적 대1례림상부의차경뇨사사진단위호박산반철탈경매결함병적환인급가계진행ALDH5A1기인돌변분석,이진일보명학진단화보조유전자순.방법 응용취합매련반응급DNA직접측서기술대1례호박산반철탈경매결함병환인급기부모적ALDH5A1기인진행돌변위점검측,동시검측100명건강대조자적ALDH5A1기인이배제다태성변이.결과 환인휴대유ALDH5A1기인편마구서렬제3외현자c.527G＞A(p.Gly176Glu)화제4외현자c.691G＞A(p.Glu231Lys)량충잡합돌변,기모친위c.527G＞A잡합돌변휴대자,부친위c.691G＞A잡합돌변휴대자.령외환인환존재량충이보도적핵산다태성개변:c.545C＞T잡합돌변화c.538C＞T순합돌변.환인적c.545C＞T돌변래원우부친,c.538C＞T돌변분별래원우부모.100명건강대조자중미검측도c.527G＞A화c.691G＞A돌변.결론 c.527G＞A(p.Gly176Glu)화c.691G＞A(p.Glu231 Lys)착의돌변가능시해환인적치병돌변.
Objective To detect potential mutation in ALDH5A1 gene for a family affected with succinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening.Methods Polymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents.Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms.Results The child was found to have carried 2 heterozygous missense mutations in the coding region of ALDH5A1 gene,namely c.527G＞ A and c.691G＞A,for which her mother and father were respectively heterozygotes.The same mutations were not detected in 100 healthy controls.The child was also found to have carried two previously described polymorphisms including a heterozygous c.545C＞T (derived from her father) and a homozygous c.538C＞T (derived from her mother).Conelusion Missense mutations of c.527G＞A and c.691G＞A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.