RESUMO
Male pseudohermaphroditism caused by steroid 5alpha-reductase deficiency is an autosomal recessive disorder. The enzyme steroid 5alpha-reductase 2 (encoded by the SRD5A2 gene) catalyses the conversion of testosterone to dihydrotestosterone, which is required for normal differentiation of the external male genitalia. This report describes the molecular analysis of the 5alpha-reductase type 2 gene in a Brazilian patient who was raised as a female, underwent a reversal of gender role behavior, and is now a married man. This patient is a compound heterozygote bearing an A-->G mutation within exon 2, changing codon 126 from Glu to Arg on one allele and a novel single base deletion (418delT) causing a frameshift mutation at codon 140 in the same exon, on the other allele. This last mutation probably leads to the synthesis of a truncated protein, because a premature termination signal is created at codon 159.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Transtornos do Desenvolvimento Sexual/genética , Mutação da Fase de Leitura , Isoenzimas/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Brasil , Códon/genética , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/enzimologia , Transtornos do Desenvolvimento Sexual/psicologia , Éxons/genética , Identidade de Gênero , Genes Recessivos , Heterozigoto , Humanos , Hipospadia/etiologia , Hipospadia/cirurgia , Recém-Nascido , Isoenzimas/deficiência , Masculino , Dados de Sequência Molecular , Fenótipo , Mutação Puntual , Puberdade , Deleção de Sequência , Comportamento Sexual , Regiões Terminadoras GenéticasRESUMO
In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.
Assuntos
17-Hidroxiesteroide Desidrogenases/deficiência , Isoenzimas/deficiência , 17-Hidroxiesteroide Desidrogenases/genética , Adulto , Transtornos do Desenvolvimento Sexual/genética , Feminino , Heterozigoto , Homozigoto , Humanos , Infertilidade Feminina/genética , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Mutação , LinhagemRESUMO
While about 40% of the South American Indian populations (Atacameños, Mapuche, Shuara) were found to be deficient in aldehyde dehydrogenase isozyme I (ALDH2 or E2), preliminary investigations showed very low incidence of isozyme deficiency among North American natives (Sioux, Navajo) and Mexican Indians (mestizo). Possible implications of such trait differences on cross-cultural behavioral response to alcohol drinking are discussed.
Assuntos
Aldeído Desidrogenase/genética , Indígenas Norte-Americanos , Indígenas Sul-Americanos , Isoenzimas/genética , Polimorfismo Genético , Aldeído Desidrogenase/deficiência , Chile , Equador , Cabelo/enzimologia , Humanos , Isoenzimas/deficiência , México , New Mexico , North DakotaRESUMO
Aldehyde dehydrogenase deficiency, N-acetyltransferase variation and the polymorphisms of alpha 1-antitrypsin, serum cholinesterase, paraoxonase, and delta-aminolevulinic acid dehydratase were investigated in 180 Atacameño Indians from the North of Chile. The genetic predisposition of these individuals for possible atypical reactions against environmental agents and drugs, as well as general implications of these findings, are discussed.