title: Genetic analysis of the SRD5A2 gene in Indian patients with 5alpha-reductase deficiency.
abstract: 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.
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sahu
authors.forename: Raman
authors.initials: R
authors.lastname: Boddula
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Bhatia
authors.forename: Ronda
authors.initials: R
authors.lastname: Greaves
authors.forename: Sudha
authors.initials: S
authors.lastname: Rao
authors.forename: Meena
authors.initials: M
authors.lastname: Desai
authors.forename: Ashish
authors.initials: A
authors.lastname: Wakhlu
authors.forename: Shubha
authors.initials: S
authors.lastname: Phadke
authors.forename: Manoj
authors.initials: M
authors.lastname: Shukla
authors.forename: Preeti
authors.initials: P
authors.lastname: Dabadghao
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Mehrotra
authors.forename: Eesh
authors.initials: E
authors.lastname: Bhatia
mesh_terms: 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
chemical_list: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase