41例5α-还原酶2型缺陷症患儿临床特点及SRD5A2基因突变分析

The phenotype and genotype characteristics of 41 patients with steroid 5α-reductase type 2 deficiency

目的探讨41例5α-还原酶2型缺陷症患儿临床表型特点及SRD5A2基因突变类型。方法收集分析患儿临床资料,包括体格检查、病史、实验室检查、B超等;并提取患儿外周血基因组DNA,采用PCR扩增产物直接测序法或靶目的基因序列捕获二代测序法检测SRD5A2基因突变类型。结果41例患儿年龄从4个月至11岁不等,汉族。所有患儿染色体核型为46,XY,SRY基因检测结果阳性。病例临床主要表现为小阴茎和尿道下裂,其中单纯表现为小阴茎的有26例,占总病例人数63%;其余15例为尿道下裂合并小阴茎,占总病例人数37%。在39例患儿中检测到双等位基因突变,2例患儿只检测到1个等位基因突变。在41例患儿中,共检测出16种基因突变类型,其中c.725A>G(p.Tyr242Cys)、c.694C>G(p.His232Asp)和c.548-9T>G这3种突变类型为未报道过的新突变。在16种突变类型中,以c.680G>A(p.Arg227Gln)为主,占所有突变类型60%(48/80)。结论5α-还原酶2型缺陷症患儿临床表现以小阴茎或尿道下裂合并小阴茎为主;c.680G>A(p.Arg227Gln)突变是中国5α-还原酶2型缺陷症患儿SRD5A2基因的热点突变类型。

Objective To investigate the clinical phenotype and the genotype of forty-one patients with steroid 5α-reductase type 2 deficiency. Methods The clinical data were collected including physical examination, medical history, laboratory test, as well as ultrasonic examination. Genomic DNA was extracted from peripheral blood leukocytes. Sanger sequencing and targeted gene captured next-generation sequencing were applied to detect the SRD5A2 gene mutation. Results All the patients are Han nationality and their ages ranged from 4 months to 11 years old. The karyotypes of 41 patients were 46, XY and all SRY genes were detected as positive. There were 26 (63%) patients manifested isolated micropenis, and the rest of fifteen patients were hypospadias associated with microphallus accounting for 37%. There were 39 patients who carried biallelic mutation. Two cases just identified one allele mutation. Sixteen gene mutation types were confirmed. Among them c. 725A>G(p.Tyr242Cys), c. 694C>G(p.His232Asp), and c. 548-9T>G are the novel gene types. The allele frequency of c. 680G>A(p.Arg227Gln) is 60%(48/80). Conclusion The primary manifestations of patients with steroid 5α-reductase type 2 deficiency were micropenis or hypospadias accompanied with micropenis. c. 680G>A(p.Arg227Gln) is the predominantly mutation type of Chinese patient with steroid 5α-reductase type 2 deficiency.