Low incidence of androgen receptor mutation among Egyptian children with androgen resistance

In Egypt, disorders of sex development [DSD] constitute a significant entity among the birth defect list. Previous studies have reported that end organ androgen unresponsiveness, i.e. Androgen resistance, was the most prevalent underlying mechanism among Egyptian 46, XY DSD cases. Based on cytogenetic and hormonal diagnostic criteria as well as few sporadic case reports, it was proposed that androgen receptor [AR] defects [i.e. Androgen insensitivity syndrome [AIS], OMIM#300068] might constitute a major etiology within this category. However, this has never been systematically ascertained through an AR molecular diagnostic approach. The current study aimed to assess the role of AR mutations as an underlying etiology among a sample of Egyptian 46,XY DSD pediatric patients presenting with androgen end organ unresponsiveness. In the current study, 21 children [age <18years] with male undermasculinization due to androgen end organ unresponsiveness were selected from 46, XY DSD cases. The selection criteria included ambiguous genital phenotype or genitalia discordant to the genotypic sex; 46,XY Karyotype and normal testicular response to HCG stimulation in prepubertal -patients or normal basal testosterone [T] levels in postpubertal subjects. Molecular studies of the AR entailed PCR amplification for screening of major deletions/ insertions, single stranded conformational polymorphism [SSCP] screening for point mutations in the AR 2-8 exons followed by sequencing of these exons for all cases. The results showed that none had major deletions/insertions. Five exons out of 147 [3.4%] showed abnormal SSCP migrational patterns. Out of those 5, two mutations in two Egyptian patients were detected by sequencing. The first was R840G [Arginine 840 glycine], in exon 7 [The ligand binding domain]. The other was A596T [Alanine 596 Threonine] in exon 3 [The DNA binding domain]. This study shows that AR mutation is an uncommon underlying etiology among Egyptian paediatric 46,XY cases

Common FGFR3 gene mutation is detected in Egyptian patients with achondroplasia phenotype

In this study, the identification of a recurrent missense mutation [G 1138 A] in the transmembrane domain of the fibroblast growth factor receptor-3 [FGFR3] protein with glycine substituted with arginine at a residue 380 [G380R] was reported. It was shown that the mutant genotype was segregated in eight sporadic cases [out of eleven] of achondroplasia patients. The identified common mutation was in the heterozygous state in all instances, the homozygous form of the mutation was not observed. The G380R was not identified in the three cases in whom the clinical and radiological features of achondroplasia were shown, indicating the possibility of the presence of another, less frequent, FGFR3 gene mutation that might account for the ACH- phenotype and need a further delineation. In this analysis, the presence of the G380R mutation in a variety of Egyptian ACH patients was confirmed, who had not been previously reported on

novel mutation in the androgen receptor gene causing partial androgen insensitivity syndrome

In the present study, a novel mutation in exon 7 of the androgen receptor [AR] gene in an Egyptian patient with partial androgen insensitivity syndrome [PAIS] was described. A male patient aged seven months was presented with ambiguous genitalia; the parents were not consanguineous. The patient had 46, XY karyotype and normal testosterone levels. Both basal and after human chorionic gonadotrophin [HCG] testosterone/dihydrotestosterone ratio was within normal suggesting normal 5-alpha reductase activity. Sequencing analysis of the AR gene revealed a novel mutation [P817A] within the ligand-binding domain [LBD]