五例17α-羟化酶缺陷症患者的CYP17A1基因突变分析

Analysis of CYP17A1 gene variants in 5 patients with 17-hydroxylase deficiency

目的 明确5例17α-羟化酶缺陷症(17-hydroxylase deficiency,17OHD)患者的致病基因及突变类型,为家系的遗传咨询提供依据.方法 应用PCR-直接测序法对5例17OHD患者和2个家系进行CYP17A1基因突变筛查,用Sanger测序对部分家系成员进行验证.结果 5例17OHD患者中,例1存在c.1459_1467del9(p.D487_F489del)和c.1244-3C>A复合杂合突变;例2~5和例3姐姐均存在c.985_987delTACinsAA(Y329Kfs)纯合突变;例2和例5家系父母和兄弟均携带c.985_987delTACinsAA(Y329Kfs)杂合突变.结论CYP 17A1基因突变是5例17OHD的致病原因,c.985_987delTACinsAA(Y329Kfs),c.1244-3C>A为新发突变.本研究结果为家系的遗传咨询提供了依据.

Objective To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency(17-OHD).Methods Peripheral blood samples were collected with informed consent.Variants of CYP17A1 gene were screened by PCR and Sanger sequencing.Suspected mutations were validated in other members of the pedigrees.Results Gene sequencing has identified a homozygous c.985_987delTACinsAA(Y329Kfs)mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3.Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9(p.D487_F489del)and c.1244-3C>A.The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs)mutation.Conclusion Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD,for which c.985_987delTACinsAA(Y329Kfs)is the most common.The c.1244-3C>A is a novel mutation.Above results have facilitated genetic counseling for the affected families.