Identification of a Rare Variant in the SRD5A2 Gene in Siblings With 46,XY Disorders of Sexual Development

The study identifies a rare homozygous variant, p.Arg246Gln, in the SRD5A2 gene in two siblings with 46,XY disorders of sexual development (DSD) from a nonconsanguineous Indian family. This variant causes 5α-reductase deficiency, leading to elevated testosterone-to-dihydrotestosterone ratios and male pseudohermaphroditism. Despite identical genotypes, the siblings exhibit different phenotypes, indicating additional modifying factors. The study emphasizes the importance of a multidisciplinary approach, including genetic diagnosis, hormonal evaluation, and personalized management strategies, in managing DSD cases. It also highlights the effectiveness of exome sequencing in diagnosing DSDs and suggests topical DHT treatment for improving penile length in affected individuals.