Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency

Fan, Lijun; Song, Yanning; Polak, Michel; Li, Lele; Ren, Xiaohan; Zhang, Beibei; Wu, Di; Gong, Chunxiu

doi:10.1002/mgg3.1431

Cited by 18 publications

(44 citation statements)

References 34 publications

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“…Patients diagnosed with 5α‐RD from March 2009 to February 2020 were included 19 . The diagnosis was made based on the clinical characteristics, the testosterone/DHT ratio, and SRD5A2 variants.…”

Section: Methodsmentioning

confidence: 99%

“…Patients diagnosed with 5α‐RD from March 2009 to February 2020 were included. 19 The diagnosis was made based on the clinical characteristics, the testosterone/DHT ratio, and SRD5A2 variants. They all carried homozygous or compound heterozygous SRD5A2 variants that were classified as pathogenic or likely pathogenic.…”

Section: Methodsmentioning

confidence: 99%

“…They all carried homozygous or compound heterozygous SRD5A2 variants that were classified as pathogenic or likely pathogenic. 19 …”

Section: Methodsmentioning

confidence: 99%

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Exploring the efficacy of testosterone undecanoate in male children with 5α‐reductase deficiency

Liu

Fan

Wang

et al. 2021

Pediatric Investigation

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Importance Children with 5‐alpha‐reductase deficiency (5α‐RD) and hypospadias present with micropenis, which makes it difficult to obtain sufficient tissue for urethral reconstruction. Objective We investigated the therapeutic effects of oral testosterone undecanoate and established a standard androgen treatment protocol for patients with 5α‐RD with micropenis. Methods Patients with 5α‐RD were treated with oral testosterone undecanoate for 3 months as a course. All patients were treated with no more than 3 courses. If the penile length (PL) reached 2.5 cm (the minimum criterion for surgery) or greater than or equal to −2.5 standard deviations (SDs) (lower limit of normal), testosterone undecanoate was considered to be effective. Results The median age of 90 patients with 5α‐RD was 1.7 years (0.9, 3.1 years). The baseline PL was 1.9 ± 0.6 cm before treatment. At the end of the first course, the PL of 63 patients (70%) reached 2.5 cm, and 49 patients (54%) reached greater than or equal to −2.5 SDs. After two treatment courses, the PL of 81 patients (90%) reached 2.5 cm, and 90 patients (100%) reached greater than or equal to −2.5 SDs. After three courses, the PL of all patients reached 2.5 cm, and all patients reached a PL greater than or equal to −2.5 SDs. No abnormal increase was observed in height‐SD score, weight‐SD score, or ratio of bone age to chronological age during the 1–3‐year follow‐up. Interpretation After 3–9 months of treatment, PL increased to the target length. No severe adverse reactions were observed during follow‐up. Testosterone undecanoate was safe and effective in children with 5α‐RD with micropenis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Exploring the efficacy of testosterone undecanoate in male children with 5α‐reductase deficiency

Liu

Fan

Wang

et al. 2021

Pediatric Investigation

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“…In 1974, 5α-RD2 was first described clinically and biochemically in studies of Dominican Republic subjects and in two siblings from Dallas, TX, United States (Imperato-McGinley et al, 1974;Walsh et al, 1974). 5α-RD2 is an autosomal recessive 46,XY DSD caused by genetic variants in the SRD5A2 gene, manifested by variable degrees of undervirilization (Fan et al, 2020). The 5α-RD2 manifests as failed or partial masculinization of external genitalia with normal Wolffian ducts, due to impaired activity of the 5-alpha reductase type 2 enzyme (3-oxo-5-alpha-steroid 4 dehydrogenase, 5α-R2).…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development

et al. 2022

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Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD.Objective: The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children.Materials and methods: The SRD5A2 gene of the parents and affected children was screened in both families via polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis.Results: Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients.Conclusion: These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior.

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“…To date, approximately 180 variants of SRD5A2 gene have been identified, with missense and nonsense mutations being the most common (Human Gene Mutation Database). The NM_000348.4:c.680G>A mutation (NP_000339.2:p.Arg227Gln) was detected in three Vietnamese patients in a homozygous state [ 5 , 8 ] and was one of the most frequent mutations in Asians [ 9 ]. In 2019, Cheng et al first reported a novel SRD5A2 mutation (NM_000348.4:c.485A>C) (NP_000339.2: p.His162Pro) in adult Chinese twins with 5 α RD2 enzyme deficiency [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

An Extremely Rare SRD5A2 Gene c.485A>C Mutation in a Compound Heterozygous Newborn with Disorders of Sex Development First Identified in Vietnam

Nguyễn

et al. 2022

Case Reports in Endocrinology

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SRD5A2 (steroid 5-alpha-reductase 2) mutation, which impairs 5α-reductase-2 enzyme activity, is among the causes of 46,XY disorders of sex development (DSD). Here, we report a rare pathogenic mutation NM_000348.4:c.485A>C (NP_000339.2:p.His162Pro) of SRD5A2 gene in a compound heterozygous state first identified in a Vietnamese newborn with 5α-reductase-2 enzyme deficiency. We also first submitted this rare mutation to ClinVar database (VCV000973099.1). The patient presented with hyperpigmented labia-majora-like bifid scrotum, clitoris-like phallus, perineoscrotal hypospadias, and blind-ending vagina. The other mutation NM_000348.4:c.680G>A (NP_000339.2:p.Arg227Gln) was reported previously. This compound heterozygous mutation was first detected by next-generation sequencing. By Sanger sequencing, we confirmed that the c.485A>C mutation was maternal inherited, whereas the c.680G>A mutation was paternal inherited. Up to date, this is the first report of this rare compound heterozygous state of SRD5A2 c.485A>C and c.680G>A mutations in patients with 46,XY DSD generally as well as in Vietnamese population particularly and is also the second report in the world carrying the pathogenic mutation NM_000348.4:c.485A>C (NP_000339.2:p.His162Pro). Our finding has enriched the understanding of the spectrum of SRD5A2 variants and phenotypic correlation in Asian patients with 46,XY DSD.

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Clinical characteristics and genotype‐phenotype correlations of 130 Chinese children in a high‐homogeneity single‐center cohort with 5α‐reductase 2 deficiency

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 34 publications

Exploring the efficacy of testosterone undecanoate in male children with 5α‐reductase deficiency

Exploring the efficacy of testosterone undecanoate in male children with 5α‐reductase deficiency

Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development

An Extremely Rare SRD5A2 Gene c.485A>C Mutation in a Compound Heterozygous Newborn with Disorders of Sex Development First Identified in Vietnam

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