46,XY disorders of sex development (DSD)

Mendonca, Berenice B.; Domenice, Sorahia; Arnhold, Ivo Jorge Prado; Costa, Elaine Maria Frade

doi:10.1111/j.1365-2265.2008.03392.x

Cited by 138 publications

(64 citation statements)

References 100 publications

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“…In our study, together with the detection of a testosterone/Δ4-androstenedione ratio elevation in 4 subjects, a definitive diagnosis was made by a molecular genetic method. In cases of 17β-HSD3 deficiency, gender identity confusion is expected because of abnormal androgen production [1,3,7,16,23]. In our study, all 6 patients with 17β-HSD3 deficiency were raised as females.…”

Section: Discussionmentioning

confidence: 90%

Rapid Molecular Genetic Diagnosis with Next-Generation Sequencing in 46,XY Disorders of Sex Development Cases: Efficiency and Cost Assessment

Özen¹,

Önay

Atik

et al. 2016

Horm Res Paediatr

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Background/Aim: The aim of this study was to use targeted next-generation sequencing (TNGS) including all known genes associated with 46,XY disorders of sex development (DSD) for a fast molecular genetic diagnosis. Methods: Twenty pediatric patients were recruited, and 56 genes related to 46,XY DSD were sequenced using TNGS. The time elapsed between initial appointment and final diagnosis as well as the mean expenditure was determined. Results: A total of 9 (45%) mutations in 4 different genes were identified. Mutations in the HSD17B3 gene were observed in 6 (30%) patients. A heterozygous mutation in WT1 gene and a hemizygous mutation in SRY gene were detected in patients with gonadal dysgenesis. One patient had a homozygous mutation in LHCGR gene. Prior to the molecular diagnosis, the mean number of clinical visits, time elapsed until diagnosis, and expenditure were 27.4 ± 14.6 visits, 5.9 ± 4.1 years per patient, and USD 2,142 ± 1,038, respectively. With TNGS, time elapsed until diagnosis was significantly reduced (3 days), and expenditure per patient was only one third of the conventional approach (USD 761). Conclusions: TNGS is an efficient, rapid, and cost-effective technique for mutation detection in 46,XY DSD.

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Section: Discussionmentioning

confidence: 90%

Rapid Molecular Genetic Diagnosis with Next-Generation Sequencing in 46,XY Disorders of Sex Development Cases: Efficiency and Cost Assessment

Özen¹,

Önay

Atik

et al. 2016

Horm Res Paediatr

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“…However, Wolffian duct development is normal, since this is dependent on testosterone, which is present at normal or high concentrations [17]. There are more than 50 families with this disorder described in several parts of the world [27]. More than 40 mutations have been reported in all five exons of the SRD5A2 gene, with some recurrent mutations (e.g., the R246W substitution) commonly reported among various ethnic groups [23,25].…”

Section: Introductionmentioning

confidence: 96%

“…Affected patients present with ambiguous external genitalia, micropenis, prostate hypoplasia, and testes with normal or reduced spermatogenesis, scarce facial and body hair, and absence of acne and temporal male baldness [10,27]. The testes are usually located in the inguinal region, suggesting that DHT influences testis migration to the scrotum [27,30]. However, Wolffian duct development is normal, since this is dependent on testosterone, which is present at normal or high concentrations [17].…”

Section: Introductionmentioning

confidence: 98%

“…The 46,XY DSD can result from mutations in the 5alpha-reductase type 2 gene (SRD5A2), located at chromosome 2p23, which encodes the steroid 5α-reductase 2 isoenzyme [27]. Steroid 5alpha-reductase converts testosterone (T) to dihydrotestosterone (DHT).…”

Section: Introductionmentioning

confidence: 99%

“…The phenotype of 5α-RD2 has been associated with mutations in the SRD5A2 gene, which includes five exons encoding a 254-amino acid protein [4,23]. Affected patients present with ambiguous external genitalia, micropenis, prostate hypoplasia, and testes with normal or reduced spermatogenesis, scarce facial and body hair, and absence of acne and temporal male baldness [10,27]. The testes are usually located in the inguinal region, suggesting that DHT influences testis migration to the scrotum [27,30].…”

Section: Introductionmentioning

confidence: 99%

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Practical approach to steroid 5alpha-reductase type 2 deficiency

Cheon

2010

Eur J Pediatr

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The aim of this article is to review the literature on steroid 5alpha-reductase type 2 deficiency (5α-RD2) to provide clinicians with information to guide their management of patients with this disorder. The 5alpha-reductase type 2 is encoded by the 5alpha-reductase type 2 gene (SRD5A2) on chromosome 2 and is predominantly expressed in external genital tissues and the prostate. Mutations of the SRD5A2 gene leads to an uncommon autosomal recessive disorder affecting sexual differentiation in individuals with 46,XY karyotype; their phenotype can range from almost normal female structures to a distinct male phenotype with ambiguous genitalia at birth. These phenotypes result from impaired conversion of testosterone to dihydrotestosterone due to mutations in the SRD5A2 gene. Patients exhibit virilization at puberty without breast development, which is often accompanied by gender identity change from female to male. More than 40 mutations have been reported in all five exons of the SRD5A2 gene. Phenotype-genotype correlations for 5α-RD2 have not been well established. The newborn phenotypes of male pseudohermaphrodites with 5α-RD2, partial androgen insensitivity syndrome (PAIS), or 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) enzyme deficiency may be indistinguishable. We conclude that steroid 5α-RD2 should be included in the differential diagnosis of newborns with 46,XY DSD. It is important that the diagnosis be made in infancy by biochemical and molecular studies before gender assignment or any surgical intervention because these patients should be considered males at birth.

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