25例尿道下裂患者的核型及SRD5A2基因突变分析

摘要

目的 对25例尿道下裂患者进行染色体核型分析及SRD5A2基因突变分析,为遗传咨询提供依据.方法 对25例尿道下裂患者进行染色体G显带核型分析及SRD5A2基因的突变分析,基因检测阳性结果者进一步进行生物信息学分析及家系分析.结果 25例患者中2例存在染色体异常,8例患者的SRD5A2基因存在复合杂合突变,临床表型均为近端型尿道下裂.涉及p.G203S/p.R227Q、p.R227Q/p.R246Q、p.Q6X/p.Q71X、p.L20P/p.G203S、p.Q71X/p.R227Q共5种基因型6种突变类型,突变率占全部尿道下裂患者的32％ (8/25),占染色体正常尿道下裂患者的35％ (8/23),占近端型尿道下裂患者的44.4％(8/18),生物信息学分析提示这些突变都具有致病性.结论 核型异常和SRD5A2基因突变是导致近端型尿道下裂的主要病因,该研究结果为患者的遗传咨询提供了依据.%Objective To analyze the karyotypes and SRD5A2 gene mutations in 25 patients with sporadic or familial hypospadias.Methods The patients included 10 adults and 15 children,whose chromosomes were analyzed by G-banded karyotyping,and the SRD5A2 genes were sequenced.Results Two patients were found to have an abnormal karyotype,while eight have carried compound heterozygous mutations of the SRD5A2 gene,which included 5 genotypes formed by 6 types of mutations,i.e.,p.G203S/p.R227Q,p.R227Q/p.R246Q,p.Q6X/p.Q71X,p.L20P/p.G203S,and p.Q71X/p.R227Q.Mutations of the SRD5A2 gene were present in 32％ (8/25) of all patients,35％ (8/23) in those with a normal karyotype,and 44.4％ (8/18) in those with proximal type hypospadia.Bioinformatic analysis,literature review and pedigree analysis confirmed that all such mutations are pathogenic.Conclusion Chromosomal anomalies and mutations of the SRD5A2 gene are the main cause of hypospadias.Sequencing of the SRD5A2 gene may explain the etiology of nearly half of the patients with proximal type of hypospadas but a normal karyotype,which can facilitate genetic consulting.