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

Autor(es)

de Calais, Flavia Leme ; Soardi, Fernanda Caroline ; Petroli, Reginaldo Jose ; Gori Lusa, Ana Leticia ; de Paiva e Silva, Roberto Benedito ; Maciel-Guerra, Andrea Trevas ; Guerra-Junior, Gil ; de Mello, Maricilda Palandi

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 12, n. 12, p. 10-pg., 2011-12-01.

Resumo

The steroid 5 alpha-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 5 alpha-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 5 alpha-reductase type II enzyme deficiency. (AU)

• Processo FAPESP: 08/01964-5 - Análise molecular do gene do receptor de andrógenos (AR) em pacientes 46,XY com ambiguidade genital e produção normal de testosterona
• Beneficiário: Reginaldo José Petroli
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/08320-9 - Investigação de mutações nos genes ar e SRD5A2 em pacientes 46,XY recém-nascidos e pré-púberes com ambiguidade genital
• Beneficiário: Maricilda Palandi de Mello
• Modalidade de apoio: Auxílio à Pesquisa - Regular