ESPE Abstracts

Aim: To study the mutation spectrum in SRD5A2 and AR genes among Indian children with 46 XY disorders of sex development (DSD).

Methods: This work is part of an ongoing study at Department of Pediatrics, AIIMS, Delhi, approved by the ethics committee of the Institute. Children with 46 XY DSD in whom endocrine investigations were suggestive of either 5α reductase deficiency or androgen insensitivity syndrome were enrolled for mutational analysis of SRD5A2 (steroid 5-alpha reductase 2) and AR (androgen receptor) genes after obtaining voluntary informed consent from the parents, and assent from children older than 12 years. Endocrine investigations including HCG stimulated testosterone and dihydrotestosterone levels were done. Bidirectional sequencing was undertaken for all 5 exons of SRD5A2 gene in 66 children. Sequencing for all 8 exons of AR gene was done in 36 of those children in whom no mutation was identified in SRD5A2.

Results: We identified mutations in 24 children (36.4%) for SRD5A2 gene, the commonest being homozygous missense mutation p.R246Q in exon 5 (in 15 children). Mutations were noted in 8 children (22.2%) for AR gene (hemizygous, as AR is located on the X chromosome), of which 2 were novel mutations not reported in HGMD, ensembl and 1000 genome data base. The clinical and endocrine parameters of the children with mutations are summarized in Table 1.

Conclusion: Mutations were identified in nearly half of the patients (32 of 66) with suspected 5α reductase deficiency or androgen insensitivity syndrome. Clinical and endocrine parameters were similar in those with mutations in either SRD5A2 or AR gene, indicating that genetic analysis is important for correct diagnosis. p.R246Q in exon 5 was a hotspot for mutations in SRD5A2 in Indian patients.