RT Journal Article SR Electronic T1 New insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype–phenotype profiling of SRD5A2 in 190 Chinese patients JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 685 OP 692 DO 10.1136/jmedgenet-2018-105915 VO 56 IS 10 A1 Baoheng Gui A1 Yanning Song A1 Zhe Su A1 Fei-Hong Luo A1 Linqi Chen A1 Xiumin Wang A1 Ruimin Chen A1 Yu Yang A1 Jin Wang A1 Xiu Zhao A1 Lijun Fan A1 Xia Liu A1 Yi Wang A1 Shaoke Chen A1 Chunxiu Gong YR 2019 UL http://jmg.bmj.com/content/56/10/685.abstract AB Background The 5α-reductase type 2 (5α-RD2) deficiency caused by mutations in the steroid 5α-reductase 2 (SRD5A2) gene results in variable degrees of undervirilisation in patients with 46,XY disorders of sex development. This study aims to profile the regional distribution and phenotype–genotype characteristics of SRD5A2 in a large Chinese 5α-RD2 deficiency cohort through multi-centre analysis.Methods 190 subjects diagnosed with 5α-RD2 deficiency were consecutively enrolled from eight medical centres in China. Their clinical manifestations and genetic variants were analysed.Results Hypospadias (isolated or combined with microphallus and/or cryptorchidism) was fairly common in the enrolled subjects (66.32%). 42 variants, including 13 novel variants, were identified in SRD5A2. Homozygous and compound heterozygous mutations presented in 38.42% and 61.58% of subjects, respectively, and predominated in exons 1, 4 and 5. The most prevalent variant was c.680G > A (52.37%), followed by c.16C > T, (10.79%), c.607G > A, (9.21%) and c.737G > A, (8.95%). However, their distributions were different: c.680G > A was more common in South China than in North China (62.62% vs 39.16%, p < 0.001), whereas the regional prevalence of c.16C > T was reversed (6.07% vs 16.87%, p = 0.001). Furthermore, c.680G > A prevailed in cases with normal meatus (68.75%) or distal hypospadias (66.28%), compared with those with proximal hypospadias (35.54%, p < 0.001). However, cases with proximal hypospadias showed a higher frequency of c.16C > T (20.48%) than those with normal meatus (3.13%) or distal hypospadias (3.49%, p < 0.001).Conclusions This study profiled variable phenotypic presentation and wide mutational spectrum of SRD5A2, revealing its distinctive regional distribution in Chinese patients and further shaping the founder effect and genotype–phenotype correlation of SRD5A2.