title: Molecular diagnosis of 5α-reductase type II deficiency in Brazilian siblings with 46,XY disorder of sex development.
abstract: 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.
authors.affiliation: Center of Molecular Biology and Genetic Engineering (CBMEG), State University of Campinas (UNICAMP), Avenida Cândido Rondon 400, 13083-875, Campinas, SP, Brazil. flaleme@unicamp.br
authors.forename: Flávia Leme
authors.initials: FL
authors.lastname: Leme de Calais
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Reginaldo José
authors.initials: RJ
authors.lastname: Petroli
authors.forename: Ana Letícia Gori
authors.initials: AL
authors.lastname: Lusa
authors.forename: Roberto Benedito
authors.initials: RB
authors.lastname: de Paiva E Silva
authors.forename: Andréa Trevas
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Júnior
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: de Mello
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000595:Amino Acid Sequence; D001665:Binding Sites; D001938:Brazil; D002648:Child; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human