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- Title
GNAS-Related Loss-of-Function Disorders and the Role of Imprinting.
- Authors
Linglart, agnès; Maupetit-Méhouas, Stéphanie; Silve, Caroline
- 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. Copyright © 2013 S. Karger AG, Basel
- Subjects
GENOMIC imprinting; PARATHYROID hormone; PSEUDOHYPOPARATHYROIDISM; G proteins; GENETIC mutation; METHYLATION; PHENOTYPES; OBESITY
- Publication
Hormone Research in Paediatrics, 2013, Vol 79, Issue 3, p119
- ISSN
1663-2818
- Publication type
Article
- DOI
10.1159/000348516