Molecular Diagnosis of 5α-Reductase Type II Deficiency in Brazilian Siblings with 46,XY Disorder of Sex Development

• Main Authors: Maricilda Palandi de Mello, Ana Letícia Gori Lusa, Gil Guerra-Júnior, Andréa Trevas Maciel-Guerra, Roberto Benedito de Paiva e Silva, Reginaldo José Petroli, Fernanda Caroline Soardi, Flávia Leme de Calais
• Format: Article
• Language: English
• Published: MDPI AG 2011-12-01
• Series: International Journal of Molecular Sciences
• Subjects: SRD5A2 deficiency; SRD5A2 gene mutations; structural analysis
• Online Access: http://www.mdpi.com/1422-0067/12/12/9471/
• ISSN: 1422-0067

The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and its deficiency leads to undervirilization in 46,XY individuals, due to an impairment of this conversion in genital tissues. Molecular analysis in the steroid 5α-reductase type II gene (SRD5A2) was performed in two 46,XY female siblings. SRD5A2 gene sequencing revealed that the patients were homozygous for p.Gln126Arg missense mutation, which results from the CGA > CAA nucleotide substitution. The molecular result confirmed clinical diagnosis of 46,XY disorder of sex development (DSD) for the older sister and directed the investigation to other family members. Studies on SRD5A2 protein structure showed severe changes at NADPH binding region indicating that structural modeling analysis can be useful to evaluate the deleterious role of a mutation as causing 5α-reductase type II enzyme deficiency.