Screening for mutations in candidate genes for hypospadias

Nordenskjöld, Agneta; Friedman, Eitan; Tappar-Persson, Margareta; Söderhäll, Cilla; Leviav, Amos; Svensson, Jan‐Olof; Anvret, Maria

doi:10.1007/s002400050088

Cited by 53 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The S597T mutation was found in 7 cases with hypospadias and cryptorchidism [17], whereas the S597G mutation was present in a patient diagnosed with PAIS [18]. This individual had two separate mutations in exon 3, S597G and in addition R617P.…”

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in the D-Box of the Androgen Receptor Gene (S597R) in Two Unrelated Individuals Is Associated with both Normal Phenotype and Severe PAIS

Giwercman¹,

Ivarsson

Richthoff³

et al. 2004

Horm Res Paediatr

View full text Add to dashboard Cite

Background: An absent or dysfunctional androgen receptor (AR) in 46,XY individuals is the most common cause of various degrees of undermasculinization. Therefore, we routinely perform sequencing of the AR gene in all cases with suspected androgen insensitivity. Methods: In a newborn 46,XY male diagnosed with partial androgen insensitivity syndrome and a phenotypically normal man, who in childhood had bilateral cryptorchidism, the AR was directly sequenced. Seven additional men with cryptorchidism in infancy were chosen as controls. Results: An AR variant (S597R) was identified in both males. Treatment of the newborn with 1% dihydrotestosterone ointment locally, resulted in normal penile size for age. Sequencing of the region in 7 other men with cryptorchidism in infancy did not reveal any additional deviation from the normal reference sequence. Conclusion: The same mutation at this codon can cause significantly different phenotypes as shown by the variation in masculinization of these individuals, with 1 severely affected child and 1 normally developed man. However, the S597R mutation does not seem to be a common cause of undescended testes in boys. Despite the S597R mutation and severe undermasculinization, as seen in the baby, normal male phenotype for age could be achieved with treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in the D-Box of the Androgen Receptor Gene (S597R) in Two Unrelated Individuals Is Associated with both Normal Phenotype and Severe PAIS

Giwercman¹,

Ivarsson

Richthoff³

et al. 2004

Horm Res Paediatr

View full text Add to dashboard Cite

show abstract

“…Because of the important role of the AR in male sex differentiation, the AR gene has been extensively examined in patients with hypospadias. Some mutations in the AR gene have been identified, but do not appear to be a frequent cause of this genital malformation (Sutherland et al, 1996;Albers et al, 1997;Nordenskjöld et al, 1999;Boehmer et al, 2001). Genetic polymorphisms are largely responsible for inter-individual differences in the ability to activate gene transcription, and therefore may influence individual susceptibility to sex differentiation disorders.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis

et al. 2015

View full text Add to dashboard Cite

ABSTRACT. Studies investigating the association between the CAG repeat polymorphism and the risk of isolated hypospadias have reported conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, CNKI, and Wanfang databases. Weighted mean difference and 95% confidence intervals for the CAG repeat polymorphism and isolated hypospadias were calculated using a random-effects model. Subgroup analyses were performed by race, study design, sample for DNA extraction, and hypospadias classifications. This meta-analysis included 6 case-control studies, including 444 isolated hypospadias cases and 727 controls. The results showed that patients with isolated hypospadias had longer CAG repeats in their androgen receptor gene sequence (weighted mean difference = 1.36, 95% confidence interval = 0.60-2.13; P = 0.0005). Similarly, stratified analyses also detected significant associations in all subgroups, excluding the group with severe hypospadias (weighted mean difference = 0.35, 95% confidence interval = -0.42-1.12; P = 0.38). This meta-analysis indicated that longer CAG repeats were 1581 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 1580-1588 (2015 CAG repeat polymorphism and isolated hypospadias associated with the risk of isolated hypospadias, and that longer CAG polymorphisms may be related to the etiology of isolated hypospadias. Future studies based on Asian and African-American patients should be performed to re-evaluate this association.

show abstract

“…In most cases it occurs sporadically, but families exist in which hypospadias segregates as a dominant trait, showing that a genetic cause is undoubtedly involved in at least a subset of cases. 2 Multifactorial models have yielded heritability indices ranging from 57 to 74% from pedigree data, indicating a multifactorial model of inheritance. 3 Normal male genital development involves a coordinated interplay between several gene products ( Figure 1), all of which are important for normal male reproductive tract development.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of five candidate genes in Chinese patients with hypospadias

et al. 2004

View full text Add to dashboard Cite

Hypospadias is the displacement of the urethral meatus from the tip of the glans to the ventral side of the phallus. During fetal development, SRY, SOX9, WT1, SRD5A2 and AR are important at different stages in the differentiation and development of the male genital system. Mutations in these genes impair masculinization and may be associated with hypospadias. In order to explore these possibilities, we employed polymerase chain reaction and direct sequencing to analyze the coding regions of these five genes in 90 Chinese hypospadias patients. We found a total of 16 different mutations in SRD5A2, AR and WT1 in 24 of these 90 patients. Seven mutations are novel. No mutation was found in SRY or SOX9. SNP V89L found in SRD5A2 was statistically significant between patients and controls. Our results indicated that mutations in SRD5A2, AR and WT1 were associated with hypospadias. In conclusion, mutations are frequently found in genes that control androgen action and metabolism, but are seldom found in genes active in the early phase of sex determination and differentiation. Mutations in AR, SRD5A2 or WT1 seem to be associated not only with hypospadias but also with micropenis.

show abstract

Screening for mutations in candidate genes for hypospadias

Cited by 53 publications

References 0 publications

A Novel Mutation in the D-Box of the Androgen Receptor Gene (S597R) in Two Unrelated Individuals Is Associated with both Normal Phenotype and Severe PAIS

A Novel Mutation in the D-Box of the Androgen Receptor Gene (S597R) in Two Unrelated Individuals Is Associated with both Normal Phenotype and Severe PAIS

Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis

Mutation analysis of five candidate genes in Chinese patients with hypospadias

Contact Info

Product

Resources

About