Audi, LFernández-Cancio, MCarrascosa, AAndaluz, PTorán, NPiró, CVilaró, EVicens-Calvet, EGussinyé, MAlbisu, M AYeste, DClemente, MHernández de la Calle, ICampo, M DelVendrell, TBlanco, AMartínez-Mora, JGranada, M LSalinas, IForn, JCalaf, JAngerri, OMartínez-Sopena, M JValle, J DelGarcía, EGracia-Bouthelier, RLapunzina, PMayayo, ELabarta, J ILledó, GSánchez Del Pozo, JArroyo, JPérez-Aytes, ABeneyto, MSegura, ABorrás, VGabau, ECaimarí, MRodríguez, AMartínez-Aedo, M JCarrera, MCastaño, LAndrade, MBermúdez de la Vega, J A2013-10-102013-10-102010-04Audi L, Fernández-Cancio M, Carrascosa A, Andaluz P, Torán N, Piró C, et al. Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development. J. Clin. Endocrinol. Metab. 2010 ; 95(4):1876-880021-972Xhttp://hdl.handle.net/10668/1323Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.en3-oxo-5-alfa-esteroide 4-deshidrogenasaExonasDisgenesia gonadal 46XYHeterocigotoIntronesMutaciónReceptores de andrógenosReacción en cadena de la polimerasa por transcriptasa inversaMedical Subject Headings::Named Groups::Persons::Age Groups::AdolescentMedical Subject Headings::Named Groups::Persons::Age Groups::ChildMedical Subject Headings::Named Groups::Persons::Age Groups::Child::Child, PreschoolMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::ExonsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::FibroblastsMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Urogenital Abnormalities::Disorders of Sex Development::46, XY Disorders of Sex Development::Gonadal Dysgenesis, 46,XYMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HeterozygoteMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Named Groups::Persons::Age Groups::InfantMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::IntronsMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, AndrogenMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain ReactionMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual BehaviorMedical Subject Headings::Anatomy::Urogenital System::Genitalia::Gonads::TestisMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-CH Group Donors::3-Oxo-5-alpha-Steroid 4-Dehydrogenaseresearch article20150575open access10.1210/jc.2009-21461945-7197