ESPE Abstracts

Background: Deficiency of microsomal membrane enzyme 5α reductase 2 impairs the DHT production and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the Genotype-Phenotype in inter-familial and intra-familial patients with same mutation of SRD5A2 gene.

Methods: All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of SRD5A2 gene.

Results: Inter-familial: Six patients from 3 families had a common p.R246Q mutation. Four patients had female sex of rearing and all of them had under gone male gender re-assignment. Two patients were reared as males. Another common combined mutation of p.V89L and IVS(1-2)T>C was present in 6 unrelated patients. Four patients had female sex of rearing and all of them under went male gender re-assignment. Two patients were reared as male. Two unrelated patients with 5αRD2 had a novel insertion of TA nucleotides in the exon 1 (188-189) of SRD5A2 gene that lead to premature termination of protein and synthesis of truncated non-functional enzyme.

Intra-familial: One family had all four children affected and the other family had two affected children. Family 1: Sequence analysis of SRD5A2 gene showed p.R246Q homozygous mutation (exon 5) in all the four siblings. Family 2: This family had two affected sibling. Sequence analysis of SRD5A2 gene showed a combined mutation of homozygous p.R246Q (exon 5) and heterozygous p.A12T (exon 1) in both the siblings.

Conclusion: The phenotype and sex of rearing was not identical in children from one family with same genotype or family environment. Though a specific genotype- phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of SRD5A2 gene may help in appropriate gender assignment.