title: Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene.
abstract: Androgen insensitivity syndrome (AIS) is caused by mutations in the androgen receptor gene and is associated with a variety of phenotypes in 46,XY individuals, ranging from phenotypic women [complete form (CAIS)] to men with minor degrees of undervirilization or infertility [partial form (PAIS)]. We studied 32 subjects with male pseudohermaphroditism from 20 families (9 CAIS, 11 PAIS) with the following criteria for AIS: 46,XY karyotype, normal male basal and human chorionic gonadotropin-stimulated levels of serum testosterone and steroid precursors, gynecomastia at puberty, and, in prepubertal patients, a family history suggestive of X-linked inheritance. The entire coding region of the androgen receptor gene was analyzed, and mutations were found in all families with CAIS and in eight of 11 families with PAIS. Fifteen different mutations were identified, including five (S119X, T602P, L768V, I898F, and P904V) that have not been described previously. Detailed clinical and hormonal features were compared with genotype in 25 subjects with AIS and confirmed by mutational analysis. LH hormone levels and the LH x testosterone product were high in all postpubertal subjects with AIS. All subjects with PAIS maintained at postpubertal age the gender identity and social sex that was assigned to them in infancy, in contrast to other forms of pseudohermaphroditism.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento e Laboratório de Hormônios e Genética Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-900, Brasil.
authors.forename: Karla F S
authors.initials: KF
authors.lastname: Melo
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ana Elisa C
authors.initials: AE
authors.lastname: Billerbeck
authors.forename: Elaine M F
authors.initials: EM
authors.lastname: Costa
authors.forename: Marlene
authors.initials: M
authors.lastname: Inácio
authors.forename: Frederico A Q
authors.initials: FA
authors.lastname: Silva
authors.forename: Angela M O
authors.initials: AM
authors.lastname: Leal
authors.forename: Ana C
authors.initials: AC
authors.lastname: Latronico
authors.forename: Ivo J P
authors.initials: IJ
authors.lastname: Arnhold
mesh_terms: D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000097:blood* / Q000235:genetics* / Q000523:psychology; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D013196:Dihydrotestosterone / Q000097:blood; D012734:Disorders of Sex Development / Q000097:blood / Q000235:genetics / Q000523:psychology; D004958:Estradiol / Q000097:blood; D005192:Family Health; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005783:Gender Identity; D006801:Humans; D007223:Infant; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D012725:Sexual Behavior; D012919:Social Behavior; D013739:Testosterone / Q000097:blood
chemical_list: D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone