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

被引：19
作者：
Gui, Baoheng [1 ]
Song, Yanning [2 ]
Su, Zhe [3 ]
Luo, Fei-Hong [4 ]
Chen, Linqi [5 ]
Wang, Xiumin [6 ]
Chen, Ruimin [7 ]
Yang, Yu [8 ]
Wang, Jin [1 ]
Zhao, Xiu [9 ]
Fan, Lijun [2 ]
Liu, Xia [3 ]
Wang, Yi [2 ]
Chen, Shaoke [10 ]
Gong, Chunxiu [2 ,11 ]
机构：
[1] Maternal & Child Hlth Hosp Guangxi Zhuang Autonom, Dept Genet & Metab, Nanning, Peoples R China
[2] Capital Med Univ, Beijing Childrens Hosp, Ctr Endocrinol Genet & Metab, Beijing 100045, Peoples R China
[3] Shenzhen Childrens Hosp, Dept Endocrinol & Metab, Shenzhen, Guangdong, Peoples R China
[4] Shanghai Jiao Tong Univ, Dept Pediat Endocrinol & Inherited Metab Dis, Shanghai, Peoples R China
[5] Soochow Univ, Childrens Hosp, Dept Endocrinol Metab & Genet Dis, Suzhou, Peoples R China
[6] Shanghai Jiao Tong Univ, Sch Med, Dept Endocrinol & Metab, Shanghai Childrens Med Ctr, Shanghai, Peoples R China
[7] Fujian Med Univ, Teaching Hosp, Fuzhou Childrens Hosp Fujian, Dept Endocrinol, Fuzhou, Fujian, Peoples R China
[8] Childrens Hosp Jiangxi Prov, Dept Endocrine Genet & Metab, Nanchang, Jiangxi, Peoples R China
[9] Shenzhen Childrens Hosp, Dept Endocrinol Metab & Genet Dis, Shenzhen, Guangdong, Peoples R China
[10] Maternal & Child Hlth Hosp Guangxi Zhuang Autonom, Dept Pediat Endocrinol, Nanning 530002, Guangxi, Peoples R China
[11] Capital Med Univ, Beijing Childrens Hosp, Beijing Key Lab Genet Birth Defects, Beijing, Peoples R China
来源：
JOURNAL OF MEDICAL GENETICS | 2019年 / 56卷 / 10期
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
MOLECULAR ANALYSIS; 46; XY DISORDERS; MALE PSEUDOHERMAPHRODITISM; V89L POLYMORPHISM; INDIAN PATIENTS; GENE; MUTATIONS; DIAGNOSIS; CHILDREN; CLASSIFICATION;
D O I：
10.1136/jmedgenet-2018-105915
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Background The 5 alpha-reductase type 2 (5 alpha-RD2) deficiency caused by mutations in the steroid 5a-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 5 alpha-RD2 deficiency cohort through multi-centre analysis. Methods 190 subjects diagnosed with 5 alpha-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.
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收藏
页码：685 / 692
页数：8
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