Novel Deleterious Mutation in Steroid-5α-Reductase-2 in 46, XY Disorders of Sex Development: Case Report Study

Abstract

Background: Steroid-5α-reductase-2 (SRD5A2) and 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) enzyme deficiencies are frequent causes of 46, XY disorder of sex development (46, XY DSD), where an infant with 46, XY has a female phenotype. We assessed the hydroxy-steroid-17β-dehydrogenase-3 (HSD17B3)and SRD5A2 genes in twenty Iranian phenotypic females with 46,XY DSD. Materials and methods: All exons in HSD17B3 and SRD5A2 genes were subjected to PCR amplification followed by sequencing. Results: Of 20 identified 46, XY DSD patients, one had a homozygous missense 17β-HSD3 mutation Ser65Leu (c.194C > T). We found 1 SRD5A2 novel homozygous missense mutation of Tyr242Asp (c.891T > G) in exon 5, which in-silico analyses revealed that this mutation may have deleterious impact on ligand binding site of SRD5A2 protein. Three other individuals harbored 17β-HSD3 deficiencies without identified mutations. Conclusions: SRD5A2 and 17β-HSD3 mutations are found in 10% of 46, XY DSD Iranian patients.

Keywords:

• Steroid 5-a reductase
• mutation
• 46 XY disorders
• sex development

Acknowledgements

We gratefully acknowledge the contribution of the scientific collaborators of the Human Genetics Department of Bu Ali Research Institute of Mashhad University of Medical Sciences.

Additional information

Funding

This study was funded by Mashhad University of Medical Sciences (grant number 931355).