Loss of Methylation at GNAS Exon A/B Is Associated With Increased Intrauterine Growth
| Autor: | Cindy Colson, Agnès Linglart, Harald Jüppner, Anne-Claire Brehin, Nicolas Richard, Virginie Grybek, Marie-Laure Kottler, Stéphanie Maupetit-Méhouas |
|---|---|
| Přispěvatelé: | Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Endocrine Unit, Massachusetts General Hospital [Boston], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Richard, Nicolas |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Clinical Biochemistry [SDV.GEN] Life Sciences [q-bio]/Genetics Biochemistry Fetal Macrosomia Fetal Development 0302 clinical medicine Endocrinology MESH: Pregnancy MESH: DNA Methylation Pregnancy GTP-Binding Protein alpha Subunits Gs Birth Weight Genetics 0303 health sciences JCEM Online: Advances in Genetics MESH: Infant Newborn MESH: Pseudohypoparathyroidism Exons Methylation Pseudohypoparathyroidism DNA methylation Female MESH: Fetal Development musculoskeletal diseases medicine.medical_specialty 030209 endocrinology & metabolism Context (language use) MESH: Syntaxin 16 Syntaxin 16 [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics Biology MESH: Chromogranins 03 medical and health sciences Internal medicine Chromogranins GNAS complex locus medicine Humans MESH: Birth Weight Retrospective Studies 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics MESH: Humans Biochemistry (medical) Infant Newborn MESH: Retrospective Studies DNA Methylation MESH: GTP-Binding Protein alpha Subunits Gs medicine.disease MESH: Male MESH: Fetal Macrosomia [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics MESH: Gene Deletion biology.protein Severe intrauterine growth retardation Pseudopseudohypoparathyroidism Genomic imprinting MESH: Exons MESH: Female Gene Deletion |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2015, 100 (4), pp.E623-E631. ⟨10.1210/jc.2014-4047⟩ Journal of Clinical Endocrinology and Metabolism, 2015, 100 (4), pp.E623-E631. ⟨10.1210/jc.2014-4047⟩ |
| ISSN: | 0021-972X 1945-7197 |
| DOI: | 10.1210/jc.2014-4047⟩ |
| Popis: | Context: GNAS is one of few genetic loci that undergo allelic-specific methylation resulting in the parent-specific expression of at least four different transcripts. Due to monoallelic expression, heterozygous GNAS mutations affecting either paternally or maternally derived transcripts cause different forms of pseudohypoparathyroidism (PHP), including autosomal-dominant PHP type Ib (AD-PHP1B) associated with loss of methylation (LOM) at exon A/B alone or sporadic PHP1B (sporPHP1B) associated with broad GNAS methylation changes. Similar to effects other imprinted genes have on early development, we recently observed severe intrauterine growth retardation in newborns, later diagnosed with pseudopseudohypoparathyroidism (PPHP) because of paternal GNAS loss-of-function mutations. Objectives: This study aimed to determine whether GNAS methylation abnormalities affect intrauterine growth. Patients and Methods: Birth parameters were collected of patients who later developed sporPHP1B or AD-PHP1B, and of their healthy siblings. Comparisons were made to newborns affected by PPHP or PHP1A. Results: As newborns, AD-PHP1B patients were bigger than their healthy siblings and well above the reference average; increased sizes were particularly evident if the mothers were unaffected carriers of STX16 deletions. SporPHP1B newborns were slightly above average for weight and length, but their overgrowth was less pronounced than that of AD-PHP1B newborns from unaffected mothers. Conclusion: LOM at GNAS exon A/B due to maternal STX16 deletions and the resulting biallelic A/B expression are associated with enhanced fetal growth. These findings are distinctly different from those of PPHP patients with paternal GNAS exons 2–13 mutations, whose birth parameters are almost 4.5 z-scores below those of AD-PHP1B patients born to healthy mothers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|