The COEXISTENCE OF MALE PSEUDOHERMAPHRODITES WITH 17‐KETOSTEROID REDUCTASE DEFICIENCY AND 5α‐REDUCTASE DEFICIENCY WITHIN a TURKISH KINDRED

Imperato‐McGinley, Julianne; Akgün, Suat; Ertel, Norman H.; Sayli, B S; Shackleton, Cedric

doi:10.1111/j.1365-2265.1987.tb00849.x

Cited by 22 publications

(12 citation statements)

References 15 publications

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“…Hormone data were consistent with the particular homozygous gene defect. An isolated Turkish kindred of male pseudohermaphrodites with biochemical evidence of two distinct enzyme defects was previously reported by this laboratory in 1987 (3). (J Clin Endocrinol Metab 83: 560 -569, 1998) A MALE pseudohermaphrodite is an incompletely masculinized individual with a 46,XY karyotype and testes.…”

mentioning

confidence: 86%

The Identification of 5α-Reductase-2 and 17β-Hydroxysteroid Dehydrogenase-3 Gene Defects in Male Pseudohermaphrodites from a Turkish Kindred1

Can

Zhu

Cai

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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Male pseudohermaphroditism (MPH) is characterized by incomplete differentiation of male genitalia in the presence of testicular tissue. Enzymatic defects involving androgen synthesis or action are causes of MPH. We studied the molecular genetics of a large isolated inbred Turkish kindred with MPH due to either 5 alpha-reductase-2 (SRD5A2) or 17 beta-hydroxysteroid dehydrogenase-3 (17 beta HSD3) gene defects. Using single strand DNA conformational polymorphism analysis and DNA sequencing, a new mutation in exon 5 of SRD5A2 gene was detected in certain male pseudohermaphrodites from this kindred. This single base deletion (adenine) resulted in a frame shift at amino acid position 251 resulting in the addition of 23 amino acids at the carboxyl-terminal of this 254-amino acid isozyme. Transfection expression of the mutant isozyme in CV1 cells showed a complete loss of enzymatic activity in the conversion of [14C]testosterone to dihydrotestosterone, without a change in the messenger ribonucleic acid level compared to that of the wild-type isozyme. Analysis of the 17 beta HSD3 gene in other male pseudohermaphrodites from this kindred revealed a single point mutation (G-->A) at the boundary between intron 8 and exon 9, disrupting the splice acceptor site of exon 9. In this kindred, in addition to the identification of male pseudohermaphrodites with either a homozygous SRD5A2 or 17 beta HSD3 gene defect, other male pseudohermaphrodites were found to be genetically more complex: e.g. homozygous for the SRD5A2 defect and heterozygous for the 17 beta HSD3 defect, or homozygous for the 17 beta HSD3 defect and heterozygous for the SRD5A2 defect. Also, phenotypically normal carriers were identified with either one or both gene defects. Homozygous male pseudohermaphrodites with SRD5A2 or 17 beta HSD3 gene defects were phenotypically distinguishable by the presence of mild gynecomastia in the latter. Hormone data were consistent with the particular homozygous gene defect. In summary, we show 1) the novel existence of two gene defects, SRD5A2 and 17 beta HSD3, each causing MPH within a large isolated Turkish kindred; 2) that the two defects segregate independently and may be inherited from two different progenitors; and 3) analysis of a new mutation in exon 5 of SRD5A2 gene, supporting the functional importance of the carboxyl-terminal of 5 alpha-reductase-2 isozyme.

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mentioning

confidence: 86%

The Identification of 5α-Reductase-2 and 17β-Hydroxysteroid Dehydrogenase-3 Gene Defects in Male Pseudohermaphrodites from a Turkish Kindred1

Can

Zhu

Cai

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Many other cases of individuals, for reasons similar to those listed previously, seemed satisfactorily to sex-reassign themselves after reaching puberty (e.g., Brown, 1964;Burns, Segaloff, & Carrera, 1960;Dewhurst & Gordan, 1969;Hoenig, 1985;Reiner, 1996;Zuger, 1970). Deserving consideration here are also the patients of Imperato-McGinley and her co-workers and other clinicians investigating situations of 5-alpha, 17-beta, and 3-beta hydroxysteroid dehydrogenase deficiency (see, e.g., Imperato-McGinley, Akgun, Ertel, Sayli, & Shackleton, 1987;ImperatoMcGinley et al, 1991;Imperato-McGinley, Peterson, Gautier, & Sturla, 1981;Rosier & Kohn, 1983). These dozens of patients were raised as girls.…”

Section: General Commentsmentioning

confidence: 97%

Sexual identity and sexual orientation in children with traumatized or ambiguous genitalia

Diamond¹

1997

Journal of Sex Research

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“…The clinical syndrome of 5-AR2 deficiency, male pseudohermaphroditism, was first discovered in the Dominican Republic22 and the United States of America 23. Subsequently, 5-AR2 deficiency syndrome was reported in many areas throughout the world 24252627. 5-AR2 deficiency is caused by mutations of the 5-AR2 gene resulting in disorders of sexual development in which 46XY men possess male internal urogenital tracts but female external genitalia 28.…”

Section: Mutation Of 5-ar Genes and Human Diseasementioning

confidence: 99%

Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications

et al. 2014

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The development of human benign or malignant prostatic diseases is closely associated with androgens, primarily testosterone (T) and dihydrotestosterone (DHT). T is converted to DHT by 5-alpha reductase (5-AR) isozymes. Differential expression of 5-AR isozymes is observed in both human benign and malignant prostatic tissues. 5-AR inhibitors (5-ARI) are commonly used for the treatment of benign prostatic hyperplasia (BPH) and were once promoted as chemopreventive agents for prostate cancer (PCa). This review discusses the role of the differential expression of 5-AR in the normal development of the human prostate and in the pathogenesis and progression of BPH and PCa.

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The COEXISTENCE OF MALE PSEUDOHERMAPHRODITES WITH 17‐KETOSTEROID REDUCTASE DEFICIENCY AND 5α‐REDUCTASE DEFICIENCY WITHIN a TURKISH KINDRED

Cited by 22 publications

References 15 publications

The Identification of 5α-Reductase-2 and 17β-Hydroxysteroid Dehydrogenase-3 Gene Defects in Male Pseudohermaphrodites from a Turkish Kindred1

The Identification of 5α-Reductase-2 and 17β-Hydroxysteroid Dehydrogenase-3 Gene Defects in Male Pseudohermaphrodites from a Turkish Kindred1

Sexual identity and sexual orientation in children with traumatized or ambiguous genitalia

Differential expression of 5-alpha reductase isozymes in the prostate and its clinical implications

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