Objective: Molecular genetics and clinical phenotypic characteristics of 5 alpha reductase deficiency were analyzed. Methods: The genetic results and clinical features classied as Prader grade of external genitalia of 86 children with SRD5A2 mutation seen from 2007 to 2017 at Department of Endocrinology of Beijing Children's Hospital were analyzed, and the mutation differences in different were compared regions according to the literatures. Results: Among the 86 children, 15 had were homozygous mutations, accounting for 17%, and 71 cases of compound heterozygous mutations accounted for 83%. Totally 172 alleles mutations in this series. The mutation was mainly located on exon 1 and exon 4, in which the mutation frequency of exon 1 was 23.8% (41/172), and the frequency of exon 4 mutation was 55.8% (96/172). A total of 19 mutation types of the SRD5A2 gene in this group were detected, of which 5 were new mutations (p.A228F, p.E57D, p.V124D, p.A117D, p.E197K); 65 patients had p.R227Q mutation, accounting for 76%, while 31 had p.Q6* mutation, accounting for 36%. Other rare types such as p.R246W, p.R103* and so on were also seen in the present study, there was no significant difference between north China and south China (P>0.05). The clinical phenotypes of p.R227Q variation varied, mainly in Prader 3-4, accounting for 82%, while (Prader 0-1) were less, accounting only 2%. The variation of p.Q6* was mainly manifested in Prader 3, accounting for 50%. p.R246Q mainly presented Prader 3. The variation of p.G203S appeared to have Prader 2 and Prader 4-5, accounting for 20% and 73% respectively. There was no significant difference in clinical phenotype corresponding to each protein type (P>0.05) . Conclusion: Among the 86 children have identified 19 SRD5A2 mutation types, p.R227Q is a hotspot mutation in Chinese. Variations at different types may have different clinical phenotypes, while the same variations may have different clinical features. There was no significance different in the variation types between the north and the south.
目的： 分析5α-还原酶缺乏症的分子遗传学和临床表型特点。 方法： 回顾性分析从2007年至2017年在首都医科大学附属北京儿童医院内分泌与遗传代谢中心就诊的86例5α-还原酶缺乏症患儿SRD5A2基因变异结果和临床表型（外生殖器表型以Prader分级）特点，并通过文献比较不同地区患儿的变异差异。 结果： 86例患儿中共有15例SRD5A2基因纯合变异（17%），71例复合杂合变异（83%）。本组共172个等位基因的变异，主要位于外显子1和外显子4上，其中外显子1变异频率为23.8%（41/172），外显子4变异频率为55.8%（96/172）。86例患儿中共检测出19种SRD5A2基因变异类型，其中5种为新发变异（p.A228F，p.E57D，p.V124D，p.A117D，p.E197K）；65例患儿有p.R227Q位点蛋白的变异（76%），31例患儿有p.Q6*蛋白变异（36%），其他少见类型如p.R246W，p.R103*等。常见蛋白变异位点的频率在我国南北方患儿比较差异无统计学意义（P>0.05）。SRD5A2基因p.R227Q蛋白变异临床表型Prader 3~4级约占82%，Prader 0~1级仅占2%；p.Q6*变异临床表型Prader3级占50%；p.R246Q变异临床表型主要为Prader 3级，表现为男性化不全（小阴茎合并尿道下裂）；p.G203S变异临床表型Prader 2级20%，Prader 4~5级73%；各变异类型对应的各临床表型例数间差异均无统计学意义（P均>0.05）。 结论： 86例患儿中共发现了19种SRD5A2基因的变异类型（含5种新发变异），76%含p.R227Q变异。不同变异会有不同的临床表型，同一变异所产生的临床表型也各不相同。各变异频率在南北方间无明显差别。.
Keywords: 5α-reductase; Genotype; Phenotype; SRD5A2 gene.