Genetic analysis of the SRD5A2 gene in Indian patients with 5alpha-reductase deficiency.
BACKGROUND
5alpha-Reductase deficiency (5RD) is an uncommon autosomal recessive disorder of sexual differentiation. It results from impaired conversion of testosterone to dihydrotestosterone due to mutations in the steroid 5alpha-reductase type 2 gene (SRD5A2). Mutations in SRD5A2 have not been previously reported in Indian patients with 5RD.


OBJECTIVE
To delineate the clinical features and mutations in the SRD5A2 gene in Indian patients with 5RD.


METHODS
The SRDSA2 gene was sequenced in two unrelated patients with elevated testosterone/dihydrotestosterone ratio and in one patient with classical clinical features and virilization at puberty (in whom the ratio could not be measured due to prior gonadectomy). The prevalence of SRD5A2 mutations was also studied in 52 healthy ethnic control subjects by PCR-RFLP.


RESULTS
Two patients, both from the north Indian state of Uttar Pradesh, carried the homozygous missense mutation p.R246Q in exon 5. Parents of both probands were heterozygous for the mutation. The mutation was absent in 52 control subjects. The third patient, with severe perineoscrotal hypospadias and micropenis, was detected to have a novel heterozygous missense mutation p.Q56H, as well as the homozygous polymorphism p.V89L, both in exon 1. The p.Q56H mutation was absent in 52 control subjects.


CONCLUSIONS
p.R246Q is a common SRD5A2 mutation in 5RD patients from the Indian subcontinent.
Sahu
Ravi
R
Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Boddula
Raman
R
Sharma
Pankaj
P
Bhatia
Vijayalakshmi
V
Greaves
Ronda
R
Rao
Sudha
S
Desai
Meena
M
Wakhlu
Ashish
A
Phadke
Shubha
S
Shukla
Manoj
M
Dabadghao
Preeti
P
Mehrotra
Ravi N
RN
Bhatia
Eesh
E
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D005836:Genitalia, Female / Q000002:abnormalities; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D014770:Virilism / Q000235:genetics* / Q000378:metabolism
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase