Heredity of Hypospadias and the Significance of Low Birth Weight

Fredell, Louise; Kockum, Ingrid; Hansson, Einar; Holmner, Staffan; Lundquist, Lars; L??CKGREN, G??RAN; PEDERSEN, J??RGEN; Stenberg, Arne; Westbacke, Gunnar; NORDENSKJ??LD, AGNETA

doi:10.1097/00005392-200203000-00069

Cited by 50 publications

(79 citation statements)

References 24 publications

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“…Like homosexuality, both traits display a familial association: when one brother in a family is affected, the prevalence is elevated in other brothers by about tenfold for hypospadias and threefold for cryptorchidism (Weidner et al 1999). Similar to homosexuality, both traits are usually not shared among monozygotic twins (approximately 25% concordance for each trait; Fredell et al 2002;Jensen et al 2010). Also like homosexuality being elevated in individuals with loss of function at the CYP21 gene (but this gene not being a major cause of female homosexuality), extensive genetic studies have found that while loss of function at some candidate genes can lead to both hypospadias and cryptorchidism, the majority of cases are not associated with any known mutations (reviewed in Bay et al 2011;Kalfa et al 2011).…”

Section: Arbitrary Traitsmentioning

confidence: 99%

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Rice

Friberg²,

Gavrilets³

2012

The Quarterly Review of Biology

113

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Section: Arbitrary Traitsmentioning

confidence: 99%

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Rice

Friberg²,

Gavrilets³

2012

The Quarterly Review of Biology

113

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“…Familial clustering of hypospadias among firstdegree relatives, as well as twin studies and segregation analysis, have supported a strong heritable component in hypospadias. Genes and environmental factors are believed to influence the risk to this disorder of the male sexual development (3,4).…”

Section: Introductionmentioning

confidence: 99%

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Beleza-Meireles

Töhönen

Söderhäll

et al. 2008

European Journal of Endocrinology

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Introduction: Hypospadias is a common inborn error of the genital development, whose complex etiology remains elusive. Defects of the androgen metabolism and activity have been found in a subset of boys with hypospadias. Moreover, the balance between androgens and estrogens seems to be important to the proper male genital development. Activating transcription factor 3 (ATF3), an estrogen responsive gene, has been reported to be expressed during sexual development and up-regulated in hypospadic genital skin. We investigated ATF3 as a candidate gene for hypospadias. Material and methods: Genotyping of eight-tagged single nucleotide polymorphisms (SNP)s was performed in 330 boys with hypospadias and in 380 healthy controls. Screening for mutations in ATF3 was conducted in a subset of boys with hypospadias. ATF3 expression was evaluated in the foreskin of boys with hypospadias and in healthy controls and in the human fetal genitalia by immunohistochemistry. Results: Three common SNPs, spanning a region of about 16 kb in intron 1 of ATF3, are associated with hypospadias. These SNPs are not linked and their effects are independent. The combination of the three risk SNPs yields the highest significance. Mutation screening identified the gene variant c536AOG in one patient and c817COT in the 3 0 -UTR in two other patients. ATF3 expression was evidenced in the developing male urethra. Conclusions: ATF3 gene variants influence the risk of hypospadias. Its hormonal responsiveness may underlie this risk effect. But also other ATF3-dependent biological aspects, such as cell survival and death, response to stress stimuli, or the control of epithelial-mesenchymal interactions, may be of importance.

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“…A family history of hypospadias increases the risk by seven-to 10-fold, suggesting an important genetic component (Brouwers et al, 2007;Fredell et al, 2002;van Rooij et al, 2013).…”

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confidence: 99%

Higher Incidence of Hypospadias in Monochorionic Twins

et al. 2015

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Background: Hypospadias is associated with twinning. The incidence of hypospadias in monochorionic and dichorionic male twins is, however, yet to be determined. Methods: All medical records of monochorionic and dichorionic twins admitted to our neonatal nursery between January 2004 and August 2013 were reviewed for the presence of hypospadias. Results: A total of 350 monochorionic and 303 dichorionic male twins were included in the study. The incidence of hypospadias in monochorionic and dichorionic groups was 4% (14/350) and 1% (3/303) (p = .016) respectively. In 11 of the 15 twin couples, hypospadias occurred in the twin with the lowest birth weight. The rate of hypospadias in twin infants small-for-gestationalage group was 10% (6/60) compared with 2% (11/593) in the appropriate-for-gestational-age group (p = .002). In a multivariate analysis, both monochorionicity and small-for-gestational-age were independently associated with hypospadias, odds ratio 4.1 (95% confidence interval (CI): 1.1-14.7) and 6.1 (95% CI: 2.2-17.2) respectively. Conclusions: The incidence of hypospadias is four-fold higher in monochorionic twins compared with dichorionic twins. Hypospadias is also independently associated with small-for-gestationalage.

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Heredity of Hypospadias and the Significance of Low Birth Weight

Cited by 50 publications

References 24 publications

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Homosexuality as a Consequence of Epigenetically Canalized Sexual Development

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Higher Incidence of Hypospadias in Monochorionic Twins

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