Introduction: 5α-Steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency. Mutations in the 5α-steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphroditism caused by decreased dihydrotestosterone (DHT) synthesis - a key hormone of virilization of male external genitalia. Aim: To study for the first time patients from the Greek Cypriot population, describe their clinical characteristics, and identify the genetic mutations of the SRD5A2 gene. Patients and methods: Three unrelated patients with 46,XY karyotype born with ambiguous genitalia were examined. Patient 1 was raised as a girl and was diagnosed with partial androgen insensitivity syndrome, based on the clinical picture and incomplete laboratory investigation at the age of 4 years, and underwent gonadectomy. For this patient sequencing analysis of all five exons of the SRD5A2 gene and exons 2 to 8 of the androgen receptor (AR) gene was performed. Patients 2 and 3 were also born with ambiguous genitalia. The hCG test for these two patients was informative of 5αSRD, as it showed elevated T/DHT ratio after stimulation. Despite genetic counseling, both families decided to raise their infants as females because of severe undervirilization. Sequencing of the SRD5A2 gene was also completed for both patients. Results: No mutations were found in the AR sequence for patient 1. Patients 1 and 3 were found homozygous for the mutation A/G at splice junction intron 1/exon 2 and patient 2 was found heterozygous for the same A/G substitution and also heterozygous for an additional mutation, Pro181Leu, in exon 3. Conclusions: The same mutation in the SRD5A2 gene was identified in three unrelated patients, in both homozygous and heterozygous form. This splice mutation was previously reported in Turkish patients. This underlying genetic abnormality may be characteristic for the Eastern Mediterranean region and is likely due to an ancestor effect.
|Number of pages||6|
|Journal||Journal of Pediatric Endocrinology and Metabolism|
|Publication status||Published - Mar 2005|
- Male pseudohermaphroditism
- SRD5A2 gene