Screening of Genital Anomalies in Newborns and Infants in Two Egyptian Governorates

Self Cite

17-β-Hydroxysteroid dehydrogenase type 3 deficiency is a rare autosomal recessive cause of 46,XY disorder of sex development. Worldwide, about 30 mutations in the hydroxysteroid (17-beta) dehydrogenase 3 (HSD17B3) gene have been reported, involving all exons except exon 1. Herein, we investigated an Egyptian female with 46,XY karyotype and low testosterone/Δ4-androstenedione ratio. Genomic DNA was extracted from blood samples, and then, direct DNA sequencing of HSD17B3 gene was performed. The patient had a homozygous mutation c.198G>A in exon 1 resulting in a stop codon (p.W50X). The study presents the first mutation to be reported in exon 1 of the HSD17B3 gene.

Section: Discussionmentioning

confidence: 90%

“…The mutations were reported in a variety of ethnic groups including those in the Mediterranean region [George et al, 2010;Ben Rhouma et al, 2012;Neocleous et al, 2012]. On the other hand, despite the relative prevalence of DSD among Egyptian patients [Mazen et al, 2010], the literature lacks reports on molecular testing of HSD17B3 gene among them.…”

mentioning

confidence: 99%

A Novel Nonsense Mutation in Exon 1 of HSD17B3 Gene in an Egyptian 46,XY Adult Female Presenting with Primary Amenorrhea

Hassan¹,

Mazen²,

Gad³

et al. 2013

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“…Partial androgen insensitivity results in hypospadias and micropenis with gynecomastia' (PAIS, MIM# 312300). The prevalence of CAIS was estimated to be 1: 20,000-99,000 within genetic males [Oakes et al, 2008] and PAIS was reported to occur with similar frequency [Mazen et al, 2010].…”

mentioning

confidence: 99%

GTG Mutation in the Start Codon of the Androgen Receptor Gene in a Family of Horses with 64,XY Disorder of Sex Development

Révay

Villagómez

Brewer

et al. 2011

Genetic sex in mammals is determined by the sex chromosomal composition of the zygote. The X and Y chromosomes are responsible for numerous factors that must work in close concert for the proper development of a healthy sexual phenotype. The role of androgens in case of XY chromosomal constitution is crucial for normal male sex differentiation. The intracellular androgenic action is mediated by the androgen receptor (AR), and its impaired function leads to a myriad of syndromes with severe clinical consequences, most notably androgen insensitivity syndrome and prostate cancer. In this paper, we investigated the possibility that an alteration of the equine AR gene explains a recently described familial XY, SRY ⁺ disorder of sex development. We uncovered a transition in the first nucleotide of the AR start codon (c.1A>G). To our knowledge, this represents the first causative AR mutation described in domestic animals. It is also a rarely observed mutation in eukaryotes and is unique among the >750 entries of the human androgen receptor mutation database. In addition, we found another quiet missense mutation in exon 1 (c.322C>T). Transcription of AR was confirmed by RT-PCR amplification of several exons. Translation of the full-length AR protein from the initiating GTG start codon was confirmed by Western blot using N- and C-terminal-specific antibodies. Two smaller peptides (25 and 14 amino acids long) were identified from the middle of exon 1 and across exons 5 and 6 by mass spectrometry. Based upon our experimental data and the supporting literature, it appears that the AR is expressed as a full-length protein and in a functional form, and the observed phenotype is the result of reduced AR protein expression levels.

“…In Egypt, a study in Great Cairo and Qalyubiyah governorates showed a relatively high incidence of 93.5 per 10,000 cases with anomalies of the external genitalia [Mazen et al, 2010]. Hypospadias is a congenital hypoplasia of the penis, with displacement of the urethral opening along the ventral surface, often associated with a dorsal hooded foreskin and chordee [van der Zanden et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Homozygous Mutation of the FGFR1 Gene Associated with Congenital Heart Disease and 46,XY Disorder of Sex Development

Mazen¹,

Amin

Kamel

et al. 2016

Congenital heart diseases (CHDs) are the most common cause of all birth defects and account for nearly 25% of all major congenital anomalies leading to mortality in the first year of life. Extracardiac anomalies including urogenital aberrations are present in ∼30% of all cases. Here, we present a rare case of a 46,XY patient with CHD associated with ambiguous genitalia consisting of a clitoris-like phallus and a bifid scrotum. Exome sequencing revealed novel homozygous mutations in the FGFR1 and STARD3 genes that may be associated with the phenotype.