Perez-Nanclares, GustavoVelayos, TeresaVela, AmayaMuñoz-Torres, ManuelCastaño, Luis2016-12-122016-12-122015-02-24Perez-Nanclares G, Velayos T, Vela A, Muñoz-Torres M, Castaño L. Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus. PLoS ONE; 10(2):e0117691http://hdl.handle.net/10668/2568Case Reports; Journal Article; Research Support, Non-U.S. Gov't;CONTEXT: Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype. OBJECTIVE: The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib. DESIGN: We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib. RESULTS: We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising ∼ 320 kb, occurred 'de novo' in the patient, whereas the other one, of ∼ 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed. CONCLUSION: In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both areassociated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.enAdultoFemeninoSubunidades alfa de la Proteína de Unión al GTP GsDuplicación de genMasculinoSeudohipoparatiroidismoAdolescenteMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding Proteins::Heterotrimeric GTP-Binding Proteins::GTP-Binding Protein alpha SubunitsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Mutagenesis::Gene DuplicationMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::PseudohypoparathyroidismMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentresearch article25710380open access10.1371/journal.pone.01176911932-6203PMC4339194