<i><scp>AR</scp></i> and <i><scp>SRD</scp>5A2</i> gene mutations in a series of 51 Turkish 46,<scp>XY DSD</scp> children with a clinical diagnosis of androgen insensitivity

Akçay, Teoman; Fernández‐Cancio, Mónica; Turan, Serap; Güran, Tülay; Audí, Laura; Bereket, Abdullah

doi:10.1111/j.2047-2927.2014.00215.x

Cited by 49 publications

(38 citation statements)

References 46 publications

(57 reference statements)

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“…At birth, these people are either diagnosed with the enzyme deficiency or misdiagnosed with androgen insensitivity syndrome [5]. However, certain genotypically male infants are born completely undervirilized and appear phenotypically female.…”

Section: Discussionmentioning

confidence: 99%

“…Androgen receptors must be present and responsive to DHT and testosterone in order for external sexual characteristics to take effect. A defect in any of the previously mentioned enzymes or hormone receptors could lead to discordance between genotype and phenotype [5].…”

Section: Introductionmentioning

confidence: 99%

“…It is an X-linked recessive disorder in which there are mutations coding for the androgen receptor leading to partial androgen insensitivity, complete androgen insensitivity or mild androgen insensitivity [5]. Partial androgen insensitivity syndrome (PAIS) is just as common as complete androgen insensitivity syndrome (CAIS), if not more [6].…”

Section: Introductionmentioning

confidence: 99%

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5-α Reductase Deficiency in Two Siblings: A Case Report

Capin

Ryan²

2016

J Med Cases

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A deficiency of 5-α reductase is a rare genetic disorder that affects 46,XY patients. The lack of enzyme causes inadequate differentiation of the gonads, leading to ambiguous genitalia or complete feminization of the external genitalia. Two sisters presented to their endocrinologist complaining of primary amenorrhea. Molecular studies revealed the SRD5A2 His231Arg gene mutation and karyotype showed 46,XY genotype. The diagnosis was supported by their high testosterone/dihydrotestosterone (DHT) ratio, response to the hCG stimulation test and their elevated sex hormone binding globulin (SHBG) levels. The siblings continued to identify as the female gender and were placed on oral premarin to develop secondary female sexual characteristics. In conclusion, any individual presenting with ambiguous genitalia, primary amenorrhea or virilization should be investigated for 5-α reductase deficiency by conducting a karyotype and full hormone profile

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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5-α Reductase Deficiency in Two Siblings: A Case Report

Capin

Ryan²

2016

J Med Cases

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“…This substitution was previously reported in several 5α-reductase-2 deficiency patients of various ethnic origin including Italy, Turkey, UK, Sweden, USA (GreekAmericans), Brazil (with European origin), Cote d'Ivoire, and India [Carpenter et al, 1990;Thigpen et al, 1992;Sinnecker et al, 1996;Nordenskjöld and Ivarsson, 1998;Hackel et al, 2005;Nicoletti et al, 2005;Baldinotti et al, 2008;Nagaraja et al, 2010, Berra at al., 2011Maimoun et al, 2011;Akcay et al, 2014]. The wide spreading of p.G196S in different ethnic groups suggests a recurrence of the mutation and a possible hot spot in SRD5A2 or a common ancestor a long time ago in human evolution.…”

Section: Discussionmentioning

confidence: 99%

New Territory for an Old Disease: 5-Alpha-Reductase Type 2 Deficiency in Bulgaria

Andonova

Robeva²,

Vazharova³

et al. 2017

Sex Dev

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Disorders/differences of sexual development (DSD) are a group of conditions, some of which can be clinically indistinguishable mainly due to their phenotypic variability. Defining the molecular basis of their wide spectrum is still in progress. The diagnosis of 5-alpha-reductase type 2 (5α-reductase-2) deficiency is difficult especially in newborns and pre-pubertal individuals, and as a result its frequency might be underestimated. In the present study, we describe the clinical characteristics and molecular defects in 3 nonrelated 5α-reductase-2 deficiency patients of Bulgarian descent. Sequencing analysis revealed the mutations p.Y188CfsX9 and p.G196S, and MLPA analysis showed a deletion of exon 1 in the SRD5A2 gene. The observed genetic substitutions were not detected in 76 additionally screened unrelated controls, but a heterozygous healthy carrier of the p.R171S mutation was found. This is the first study on the molecular basis of 5α-reductase-2 deficiency in Bulgaria. It suggests that the carrier frequency of mutations in the SRD5A2 gene might be noteworthy worldwide. There is no correlation between cultural aspects, location, and/or population size and the number of different mutations in SRD5A2 detected, and more efforts should be made to determine the prevalence of this condition in different geographic areas. Our study supports the importance of genetic testing in 46,XY DSD patients, especially in countries or regions where 5α-reductase-2 deficiency has not been reported so far.

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“…Through the chi-square test, there was no statistical difference between experimental and control groups. Other research has found that c.265C > G and p.L89V mutations were related to sperm quality (Massanyi et al, 2013), severe hypospadias (Akcay et al, 2014), and prostate cancer risk (Gottlieb et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Correlation of androgen receptor and SRD5A2 gene mutations with pediatric hypospadias in 46, XY DSD children

Zhang

2016

Genet. Mol. Res.

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ABSTRACT. We performed an exploratory study by analyzing the correlation of 46, XY disorders of sex development (46, XY DSD) with androgen receptor (AR) and steroid 5α-reductase-2 (SRD5A2) gene mutations and a safety analysis of dihydrotestosterone (DHT) gel treatment for pediatric micropenis. We collected samples from 76 pediatric patients with 46, XY DSD and 50 healthy adult men with normal fertility as the control group. The pediatric patients were treated with DHT gel (0.1-0.3 mg/kg/day) for three to six months. The extended penis length, testicular volume, and multiple blood parameters were collected before treatment and one, three, and six months after treatment. Of the 76 cases with 46, XY DSD, 31.58% had hypospadias with micropenis and 6.58% had male pseudohermaphroditism. Through AR gene screening, it was found that 14 patients had AR point mutations and 22 patients had SRD5A2 mutations. After treatment with DHT, the penis length of the patients significantly improved after one, three, and six months of treatment, with longer treatment times resulting in greater improvement. Before treatment with DHT, the average serum DHT value of patients with 46, XY DSD was 24.29 pg/mL. After one, three, and six months of treatment, this value increased to 430.71, 328.9, and 323.6 pg/mL, respectively. We conclude that for pediatric patients who have male hermaphroditism or hypospadias with micropenis, AR and SRD5A2 gene mutation detection should be performed. Local application of DHT gel can promote penis growth effectively without systemic adverse reactions.

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AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity

Cited by 49 publications

References 46 publications

5-α Reductase Deficiency in Two Siblings: A Case Report

5-α Reductase Deficiency in Two Siblings: A Case Report

New Territory for an Old Disease: 5-Alpha-Reductase Type 2 Deficiency in Bulgaria

Correlation of androgen receptor and SRD5A2 gene mutations with pediatric hypospadias in 46, XY DSD children

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