Molecular analysis of 5α-reductase type 2 gene in eight unrelated egyptian children with suspected 5α-reductase deficiency: Prevalence of the G34R mutation

OBJECTIVE: Analysis of the 5α-reductase type 2 (SRD5A2) gene in Egyptian patients with suspected 5α-reductase (5αR) deficiency. PATIENTS AND METHODS: Eight unrelated patients, originating from different geographical areas of Egypt, were referred to the Department of Pediatrics. Six prepubertal and two postpubertal patients presented with ambiguous genitalia. Four were being reared as females while the others were being reared as males. Six patients were products of consanguineous marriages. All patients had 46,XY karyotype. Basal and post-human chorionic gonadotrophin (hCG) stimulation plasma levels of testosterone and dihydrotestosterone were determined. Sequencing of five exons of the SRD5A2 gene was carried out. RESULTS: All patients had normal male testosterone levels, both basal and post-hCG stimulation. The T/DHT ratio was available for six patients and showed values that ranged from normal to high. Three different homozygous mutations were identified. One patient carried aY235F substitution and two had a N160D substitution. Interestingly, all five of the other patients had the G34R mutation. The parents were heterozygous for the mutations, although the mother of one patient was homozygous for the G34R mutation. CONCLUSION: Among eight unrelated Egyptian children with 5α-reductase deficiency, the G34R mutation was identified in five patients. The high consanguinity rate in Egypt suggests a common ancestor with a founder gene effect in cases of G34R mutation.