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：22

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.

引用

页码：685 / 692

页数：8

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