title: GNAS -Related Loss-of-Function Disorders and the Role of Imprinting.
abstract: GNAS (guanine nucleotide-binding protein, α stimulating) is a complex imprinted locus coding, besides the α-stimulatory subunit of the G protein, the paternally (extra-large, antisense and A/B) and maternally (neuroendocrine secretory protein) transcripts. Heterozygous mutations in the coding sequence of GNAS produce dominant phenotypes (combination of resistances to hormones signaling through G-protein-coupled receptors, osteodystrophy and obesity) that depend on the parental origin of the mutated allele. Likewise, alterations in the methylation at promoters of GNAS transcripts, associated or not with deletions of imprinting control regions in the nearby STX16 gene or within GNAS, prompt resistance to parathormone when affecting the maternal allele. Therefore, imprinting of GNAS is the determining factor for the variability of the phenotype. Knowledge of the various phenotypes is necessary for genetic counseling as well as an appropriate therapeutic balance between regular follow-up, prevention of disease complications and iatrogeny.
authors.affiliation: Endocrinology and Diabetology for Children and French Center of Reference for Rare Disorders of Calcium and Phosphorus Metabolism, Bicêtre-Paris-Sud Hospital, Le Kremlin Bicêtre, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Maupetit-Méhouas
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
mesh_terms: D000483:Alleles; D002864:Chromogranins; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism; D018392:Genomic Imprinting; D006801:Humans; D009154:Mutation; D016366:Open Reading Frames; D051438:Syntaxin 16 / Q000235:genetics / Q000378:metabolism
chemical_list: D002864:Chromogranins; C496118:STX16 protein, human; D051438:Syntaxin 16; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs