Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development

Abstract Objectives 5α-reductase type 2 deficiency due to biallelic SRD5A2 variants is a common form of 46,XY disorders of sex development. Case presentation A Chinese neonate presented with ambiguous genitalia. He carried a homozygous likely_pathogenic SRD5A2 variant (c.650C>A, p.A217E). His apparently nonconsanguineous parents were heterozygotes for the variant. The variant has previously been identified in two Chinese patients. Our patient carried 14.2 Mb loss-of-heterogeneity regions distributed in the genome. The SRD5A2 variant in this family was invariably coupled with two polymorphisms in exon 1 and intron 1. In the patient, blood testosterone (T)/5α-dihydrotestosterone (5αDHT) ratios were elevated before and during mini puberty, and were higher when measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) than measured by conventional immune assays. Conclusions This study provides evidence for the founder effect of an SRD5A2 variant. Furthermore, our data indicate that there is a need to establish a new reference value for T/5αDHT ratios using LC-MS/MS.

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The Investigation of Quality of Life in 87 Chinese Patients with Disorders of Sex Development

BioMed Research International ◽

10.1155/2015/342420 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Chunqing Wang ◽

Qinjie Tian

Keyword(s):

Quality Of Life ◽

Social Relationship ◽

Disorders Of Sex Development ◽

Androgen Insensitivity Syndrome ◽

Chinese Patients ◽

Sexual Life ◽

Process Of Care ◽

Sex Development ◽

The Difference

Objective. In the process of care for disorders of sex development (DSD), clinical decisions should focus on the long-term quality of life (QOL). We sought to investigate the QOL of patients with DSD in China.Design. Case-control study was carried out.Patients.90 patients of DSD participated in the study. Finally, 87 patients were analyzed including Turner’s syndrome (23), Noonan syndrome (2), androgen insensitivity syndrome (22), testicular regression syndrome (2), congenital adrenal hyperplasia (16), and pure gonadal dysgenesis (22).Measurements. The WHOQOL-BREF questionnaire was chosen for the present investigation. Four domain scores were analyzed independently including physical, psychological, and social relationship and environmental domains.Results. The average age of the DSD group is 22.34 ± 4.97 years, and only 13.79% patients ever had sexual life. The scores of psychological and environmental domains were lower than that of the physical and social relationship domains, but the difference was not significant (P>0.05). Compared with the Chinese urban population, the QOL scores of DSD patients in China were not significantly lower.Conclusions. With proper treatment, including the follow-up and psychological support, the QOL of DSD patients cannot be significantly reduced. For DSD patients, more attention should be paid to the potential psychological and sexual problems.

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Two novel mutations in theNR5A1gene as a cause of disorders of sex development in a Pakistani cohort of 46,XY patients

Andrologia ◽

10.1111/and.12470 ◽

2015 ◽

Vol 48 (5) ◽

pp. 509-517 ◽

Cited By ~ 4

Author(s):

S. Hussain ◽

A. Amar ◽

M. N. Najeeb ◽

S. Khaliq

Keyword(s):

Disorders Of Sex Development ◽

Novel Mutations ◽

Sex Development

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A large cohort of disorders of sex development and their genetic characteristics: 6 novel mutations in known genes

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2021.104154 ◽

2021 ◽

Vol 64 (3) ◽

pp. 104154

Author(s):

Aysun Ata ◽

Samim Özen ◽

Hüseyin Onay ◽

Selin Uzun ◽

Damla Gökşen ◽

...

Keyword(s):

Disorders Of Sex Development ◽

Large Cohort ◽

Novel Mutations ◽

Genetic Characteristics ◽

Sex Development

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Novel NR5A1 mutations found in Chinese patients with 46, XY disorders of sex development

Clinical Endocrinology ◽

10.1111/cen.13831 ◽

2018 ◽

Vol 89 (5) ◽

pp. 613-620 ◽

Cited By ~ 1

Author(s):

Bingqing Yu ◽

Zhaoxiang Liu ◽

Yinjie Gao ◽

Jiangfeng Mao ◽

Xi Wang ◽

...

Keyword(s):

Disorders Of Sex Development ◽

Chinese Patients ◽

Sex Development

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Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0048 ◽

2017 ◽

Vol 30 (1) ◽

Cited By ~ 4

Author(s):

Chupong Ittiwut ◽

Jaturong Pratuangdejkul ◽

Vichit Supornsilchai ◽

Sasipa Muensri ◽

Yodporn Hiranras ◽

...

Keyword(s):

Disorders Of Sex Development ◽

External Genitalia ◽

Mendelian Inheritance ◽

Novel Mutations ◽

Cross Sectional ◽

Genetic Characteristics ◽

Reductase Deficiency ◽

Testosterone Production ◽

Sex Development ◽

5Α Reductase Deficiency

AbstractBackground:Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th–12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD.Methods:A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of theResults:Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations inConclusions:Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of

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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

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105915 ◽

2019 ◽

Vol 56 (10) ◽

pp. 685-692 ◽

Cited By ~ 2

Author(s):

Baoheng Gui ◽

Yanning Song ◽

Zhe Su ◽

Fei-Hong Luo ◽

Linqi Chen ◽

...

Keyword(s):

Regional Distribution ◽

Clinical Manifestations ◽

Disorders Of Sex Development ◽

Chinese Patients ◽

Compound Heterozygous ◽

Multi Centre Study ◽

Proximal Hypospadias ◽

Sex Development ◽

Distal Hypospadias

BackgroundThe 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.Methods190 subjects diagnosed with 5α-RD2 deficiency were consecutively enrolled from eight medical centres in China. Their clinical manifestations and genetic variants were analysed.ResultsHypospadias (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).ConclusionsThis 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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