Carriers for type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by <i>HSD3B2</i> genotype study and not by hormone test

Pang, Songya; Carbunaru, Goldy; Haider, Anzar; Copeland, Kenneth C.; Chang, Ying; Lutfallah, Chantal; Mason, J. Ian

doi:10.1046/j.1365-2265.2003.01716.x

Cited by 21 publications

(9 citation statements)

References 49 publications

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“…Increased levels of adrenal androgens and hypersensitivity to steroid hormones are proposed to cause PP. Mutations of CYP21A2 and HSD3B2 genes have been described in PP patients [ 22 – 24 ]. The mechanism of disease is also still not understood completely, but 21-OH, 17-OH, and 17, 20-lyase and 3B-HSD are involved in the processes leading to puberty [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Soveizi

Mahdieh

Setoodeh

et al. 2020

International Journal of Endocrinology

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Premature pubarche (PP) is the appearance of sexual hair in children before puberty. The PP phenotype may attribute to nonclassic congenital adrenal hyperplasia (NC-CAH). In this study, we investigated the role of CYP21A2 gene variants in patients with PP in the Iranian population. Forty patients (13 males and 27 females), clinically diagnosed with PP, were analyzed for molecular testing of CYP21A2 gene variants. Direct sequencing was performed for the samples. Also, gene dosage analysis was performed for the cases. Fourteen patients (35%) had a mutation of p.Gln318X and p.Val281Leu, out of which 10% had regulatory variants. Approximately 10% of the patients were homozygous (NC-CAH). 78.5% (11/14) of patients had trimodular RCCX of which 5 patients had two copies of CYP21A1P pseudogene. The prevalence of p.Val281Leu was higher than p.Gln318X in PP patients. In conclusion, CYP21A2 variant detection has implications in the genetic diagnosis of PP phenotype. The genetic characterization of the CYP21A2 gene is important for characterizing the variable phenotype of carriers and genetic counseling of PP and NC-CAH patients.

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Section: Discussionmentioning

confidence: 99%

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Soveizi

Mahdieh

Setoodeh

et al. 2020

International Journal of Endocrinology

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“…Interestingly, several other AAD patients included in our exome sequencing analysis carry rare heterozygous non-synonymous variants in HSD3B2 (Table 2). Although it appears that family members of CAH patients, carrying heterozygous HSD3B2 mutations, maintain normal 3βHSD2 activity in vivo (14), genetic variations in HSD3B2 are associated with other conditions such as idiopathic hypospadias and prostate cancer (15, 16). Therefore, both subtle molecular abnormalities and deleterious mutations in HSD3B2 could have biological consequences, and may play a role in the pathogenesis of the immune-mediated adrenocortical destruction in AAD.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of Congenital Adrenal Hyperplasia and Autoimmune Addison's Disease

et al. 2019

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Background: Underlying causes of adrenal insufficiency include congenital adrenal hyperplasia (CAH) and autoimmune adrenocortical destruction leading to autoimmune Addison's disease (AAD). Here, we report a patient with a homozygous stop-gain mutation in 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2), in addition to impaired steroidogenesis due to AAD.Case Report: Whole exome sequencing revealed an extremely rare homozygous nonsense mutation in exon 2 of the HSD3B2 gene, leading to a premature stop codon (NM_000198.3: c.15C>A, p.Cys5Ter) in a patient with AAD and premature ovarian insufficiency. Scrutiny of old medical records revealed that the patient was initially diagnosed with CAH with hyperandrogenism and severe salt-wasting shortly after birth. However, the current steroid profile show complete adrenal insufficiency including low production of pregnenolone, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S), without signs of overtreatment with steroids.Conclusion: To the best of our knowledge, this is the first description of autoimmune adrenalitis in a patient with 3βHSD2 deficiency and suggests a possible association between AAD and inborn errors of the steroidogenesis.

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“…administration of synthetic ACTH with measurement of 17-OHpreg, cortisol, Δ4-17-OHP, DHEA, and androstenedione [7]. Steroidal responses to ACTH cannot reliably identify heterozygous carriers of 3β-HSD deficiency [45].…”

Section: 3β-hydroxysteroid Dehydrogenase Type 2 Deficiency (3β-hsd2d)mentioning

confidence: 99%

46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

Baronio

Ortolano

Menabò

et al. 2019

IJMS

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The term ‘differences of sex development’ (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46,XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment.

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Carriers for type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test

Cited by 21 publications

References 49 publications

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Coexistence of Congenital Adrenal Hyperplasia and Autoimmune Addison's Disease

46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features

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