The IVS1-2A>G mutation in the SRD5A2 gene predominates in Cypriot patients with 5α reductase deficiency

Background: 5 alpha steroid reductase deficiency (5 alpha SRD) is an autosomal recessive enzymatic deficiency and mutations in the 5 alpha steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis. Aim: To identify the specific mutations of the SRD5A2 gene in Cypriot patients with 5 alpha SRD. Subjects and methods: Five unrelated patients with 46,XY karyotype were examined. Four of them were born with ambiguous genitalia and 1 patient, who was raised as girl, presented with primary amenorrhea. The hCG test was informative (elevated testosterone/DHT) of 5 alpha SRD in 3 out of 4 subjects. Sequencing of the SRD5A2 gene was completed for all patients. Genomic DNA was also isolated from a total of 204 healthy unrelated Cypriot subjects. Screening for the IVS1-2A > G mutation was performed by using direct sequencing and restriction enzyme analysis. Results: The IVS1-2A > G was identified in homozygosity in 3 patients and in a compound heterozygote state in the other 2 patients, in combination with p.P181L and p.R171S in exon 3, respectively. The carrier frequency in the Cypriot population for the IVS1-2A > G mutation was estimated to be 0.98% or 2 in 204. Conclusions: The same IVS1-2A > G mutation in the SRD5A2 gene seems to characterize all Cypriot patients with 5 alpha SRD diagnosed so far. Furthermore this relatively rare genetic defect, which has only been reported previously in a single case in the Eastern Mediterranean region, is very likely to be the result of a founder effect. (J. Endocrinol. Invest. 33: 810-814, 2010) (C) 2010, Editrice Kurtis