Molecular Characterization of Steroid 5 Alpha-Reductase 2 (SRD5A2) Gene Variant in Indian Patients with Disorder of Sexual Development

The 5 alpha-reductase deficiency is one of the significant causes of the disorders of sex development (DSD) in individuals bearing 46 XY chromosomes. The conversion of testosterone into dihydrotestosterone is impaired on account of this enzyme deficiency. The mutations in the steroid 5 alpha-reductase type 2 gene (SRD5A2) result in the deficiency of this enzyme. We hereby report three cases of DSD presented in the Pediatric Department of Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab. The current study was carried out to identify the subtype of DSD in children born to non-consanguineous parents of two families recruited from South West Punjab. Proband 1, belonging to Family 1, was 4.5 years old, whereas Probands 2 and 3 from Family 2 were siblings of 4 years and 2 years of age. All the patients presented with clitoral enlargement and other features, including palpable swellings in the labia majora and bilateral labioscrotal folds. The DNA of the affected children was subjected to exome sequencing. All three were found to be homozygous for c.737G > A: p.R246Q alteration. This was confirmed by Sanger Sequencing and, at the same time, parents were found to be heterozygous. The clinical examination, radiological investigation, hormonal profiling, and the mutation confirmed that all the probands were affected with pseudo vaginal perineoscrotal hypospadias, a subtype of DSD.