&lt;p&gt;Integrative and Analytical Review of the 5-Alpha-Reductase Type 2 Deficiency Worldwide&lt;/p&gt;

Batista, Rafael Loch; Mendonca, Berenice B.

doi:10.2147/tacg.s198178

Cited by 30 publications

(25 citation statements)

References 104 publications

(171 reference statements)

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“…Even in the absence of dihydrotestosterone, the presence of androgens usually directs towards male psychosexuality development. This could explain the relatively high rate of gender change from female to male in 5 α RD2 deficiency, estimated 56–63% [ 18 , 19 ]. Because our patient was diagnosed early and was raised as a male, the conflict in identifying sex will be avoided.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…DHT plays very important roles in mammalian sex differentiation as the most potent androgen ( 4 ). Mutations of the SRD5A2 gene cause 46, XY disorders of sex development, resulting from low DHT production ( 4 , 8 ). In contrast, little attention has been received in the existence and functions of DHT in fish, because it is thought to be relatively biologically inactive.…”

Section: Discussionmentioning

confidence: 99%

“…SRD5A2 is strongly expressed in male tissues, including prostate and epididymis for producing DHT during development (4). Therefore, mutations of the SRD5A2 gene cause 46, XY disorders of sex development, resulting from low DHT production (5)(6)(7)(8). SRD5A1 mainly plays roles in the production of neurosteroids involved in anxiety and sexual behavior (4).…”

Section: Introductionmentioning

confidence: 99%

Profiles of 5α-Reduced Androgens in Humans and Eels: 5α-Dihydrotestosterone and 11-Ketodihydrotestosterone Are Active Androgens Produced in Eel Gonads

et al. 2021

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Although 11-ketotestosterone (11KT) and testosterone (T) are major androgens in both teleosts and humans, their 5α-reduced derivatives produced by steroid 5α-reductase (SRD5A/srd5a), i.e., 11-ketodihydrotestosterone (11KDHT) and 5α-dihydrotestosterone (DHT), remains poorly characterized, especially in teleosts. In this study, we compared the presence and production of DHT and 11KDHT in Japanese eels and humans. Plasma 11KT concentrations were similar in both male and female eels, whereas T levels were much higher in females. In accordance with the levels of their precursors, 11KDHT levels did not show sexual dimorphism, whereas DHT levels were much higher in females. It is noteworthy that plasma DHT levels in female eels were higher than those in men. In addition, plasma 11KDHT was undetectable in both sexes in humans, despite the presence of 11KT. Three srd5a genes (srd5a1, srd5a2a and srd5a2b) were cloned from eel gonads. All three srd5a genes were expressed in the ovary, whereas only both srd5a2 genes were expressed in the testis. Human SRD5A1 was expressed in testis, ovary and adrenal, whereas SRD5A2 was expressed only in testis. Human SRD5A1, SRD5A2 and both eel srd5a2 isoforms catalyzed the conversion of T and 11KT into DHT and 11KDHT, respectively, whereas only eel srd5a1 converted T into DHT. DHT and 11KDHT activated eel androgen receptor (ar)α-mediated transactivation as similar fashion to T and 11KT. In contrast, human AR and eel arβ were activated by DHT and11KDHT more strongly than T and 11KT. These results indicate that in teleosts, DHT and 11KDHT may be important 5α-reduced androgens produced in the gonads. In contrast, DHT is the only major 5α-reduced androgens in healthy humans.

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“…A recent interesting review on SRD5A2 mutations found that exon 1 and 4 accounted for about 58% of all mutations reported in this gene and that five hotspots 55, 65, 196, 235 and 246 accounted for up to 25% allelic variants (Batista & Mendonca, 2020). G196S has emerged as a mutation hotspot in the SRD5A2 gene and has been described in Greek, Turkish, Swedish and Brazilian, American, European and Asian populations (Batista & Mendonca, 2020). This mutation has been shown to result in a consistent phenotype irrespective of the population where it was reported.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identified compound heterozygous mutations in theSRD5A2gene in a case of 46,XY ambiguous genitalia

Mehta

Rajender

2020

Andrologia

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Differentiation of the bi-potential gonad into testes or ovaries is driven by the chromosome complement of the foetus. It is believed that the differentiation into ovaries is a default setting, which in the presence of SRY gets diverted to testicular development. Chromosomal anomalies at this stage or mutations in the SRY gene or its translocation to the X-chromosome gives rise to an array of ambiguous gonad phenotypes, resulting in partial to complete discordance between the chromosome complement and the gonadal sex (Mendonca et al., 2009). Once the gonads are differentiated, the production of testosterone by the testis drives the differentiation of the external genitals into male, the absence of which would result in their development into female external genitals (Arnold, 2017). However, errors in testosterone production or the failure of its action due to mutations in the androgen receptor (AR) may result in the development of the external genitals in contrast to the chromosomal complement. In genetic males, testosterone is converted into dihydrotestosterone (DHT) by SRD5A2 protein, encoded by the SRD5A2 gene. DHT production is essential as its drives the differentiation of the external male genitals. The lack of testosterone production, failure of its conversion into DHT or failure of their action due to AR mutations results in an array of ambiguous genitalia phenotypes, named as the disorders of sexual development (DSD) (Rajender et al., 2007). Ambiguous external genitalia are a rare phenotype where genitals cannot be distinguished as a male or a female. This uncertainty about

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<p>Integrative and Analytical Review of the 5-Alpha-Reductase Type 2 Deficiency Worldwide</p>

Cited by 30 publications

References 104 publications

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

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

Profiles of 5α-Reduced Androgens in Humans and Eels: 5α-Dihydrotestosterone and 11-Ketodihydrotestosterone Are Active Androgens Produced in Eel Gonads

Exome sequencing identified compound heterozygous mutations in theSRD5A2gene in a case of 46,XY ambiguous genitalia

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