ESPE Abstracts (2018) 89 P-P3-342

Characterization of Genotype-Phenotype in Inter-Familial and Intra-Familial Patients with Same Mutation of SRD5A2 Gene

Iram Shabir, Rajesh Khadgawat, Rima Dada & Viveka P. Jyotsna


All India Institute of Medical Sciences, New Delhi, India.


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.

Article tools

My recent searches

No recent searches.