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

N. Skordis, V. Neocleous, A. Kyriakoui, E. Efstathiou, A. Sertedaki, P. Philibert, L. A. Phylactou, S. Lumbroso, C. Sultan

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 5α steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency and mutations in the 5α 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 5αSRD. 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 5αSRD 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 5αSRD 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.

Original languageEnglish
Pages (from-to)810-814
Number of pages5
JournalJournal of Endocrinological Investigation
Volume33
Issue number11
DOIs
Publication statusPublished - Dec 2010

Keywords

  • 46,XY disorders of sexual development (DSD)
  • 5α-reductase
  • Male pseudohermaphroditism
  • Mutations
  • SRD5A2 gene

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