A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family.
OBJECTIVE
To analyze the steroid 5-alpha reductase type 2 gene (SRD5A2) in 2 siblings with severe male pseudohermaphroditism suspected to have 5-alpha reductase deficiency in a Turkish family.


METHODS
Two female siblings of a family with 7 children were referred to the urology department because of bilateral inguinal masses. The patients had presented after birth with ambiguous genitalia, but no further diagnostic procedures had been performed, and they were raised as girls until the ages of 13 and 15 years. At this time, both had striking ambiguity of the genitalia, with a clitoris-like phallus, severely bifid scrotum, pseudovaginal perineoscrotal hypospadias, a rudimentary prostate, and inguinal testes. Karyotype was 46,XY. Basal and stimulated levels of serum testosterone (T), dihydrotestosterone (DHT), and T/DHT ratio indicated 5-alpha reductase deficiency. Molecular genetic analysis was performed on deoxyribonucleic acid from peripheral blood leukocytes by single-stranded conformational polymorphism analysis and direct sequencing.


RESULTS
Analysis of the SRD5A2 gene revealed a new homozygous missense mutation in exon 2. At codon 123, we identified a GGA to AGA change resulting in a missense amino acid change from glycine to arginine (G123R). Both parents and the 2 healthy sisters and 3 brothers were all heterozygous at codon 123 for the same mutation.


CONCLUSIONS
We report a novel homozygous missense mutation in exon 2 of the 5-alpha reductase type 2 gene that led to severe undervirilization in 2 siblings.
Bahceci
Mithat
M
Department of Endocrinology, University of Dicle, School of Medicine, Diyarbakir, Turkey. mbahceci@dicle.edu.tr
Ersay
Ahmet Resit
AR
Tuzcu
Alpaslan
A
Hiort
Olaf
O
Richter-Unruh
Annette
A
Gokalp
Deniz
D
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000293:Adolescent; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D012720:Severity of Illness Index; D014421:Turkey
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase