Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Endocrinology and Metabolism Année : 2018

Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome

1 CRSA - Centre de Recherche Saint-Antoine
2 CHU Trousseau [APHP]
3 U933 - Maladies génétiques d'expression pédiatrique
4 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
5 CHU Pitié-Salpêtrière [AP-HP]
6 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
7 Département de génétique médicale [Hôpital de la Timone - APHM]
8 FMUSP - Universidade de São Paulo Medical School
9 Hôpital Necker - Enfants Malades [AP-HP]
10 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
11 Service de pédiatrie générale [CHU Necker]
12 IGDR - Institut de Génétique et Développement de Rennes
13 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
14 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
15 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
16 CHU Montpellier
17 UM - Université de Montpellier
18 CHU Nantes - Centre Hospitalier Universitaire de Nantes
19 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
20 U 1169 - Thérapie génique, Génomique et Epigénomique
21 UBS Lorient - Université de Bretagne Sud - Lorient
22 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
23 Service de Génétique Médicale [CHU Necker]
24 UPD5 - Université Paris Descartes - Paris 5
25 USPC - Université Sorbonne Paris Cité
26 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
27 SPCTS-AXE3 - Axe 3 : organisation structurale multiéchelle des matériaux
28 SPW-PRADORT - Centre de Référence du Syndrome de Prader-Willi [CHU Toulouse]
29 GAD - Génétique des Anomalies du Développement
30 MSSM - Icahn School of Medicine at Mount Sinai [New York]
31 INSERM - Institut National de la Santé et de la Recherche Médicale
32 SU - Sorbonne Université
Virginie Steunou
  • Fonction : Auteur
  • PersonId : 906460
Solveig Heide
Agnès Linglart
Julien Thevenon
  • Fonction : Auteur
  • PersonId : 964270
Jennifer Salem
  • Fonction : Auteur

Résumé

Context - Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with phenotypic (prenatal and postnatal growth retardation, early feeding difficulties) and molecular overlap. Objective - To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS. Patients - We retrospectively collected data on 28 patients with disruption of the 14q32.2 imprinted region, identified in our center, and performed extensive molecular analysis. Results - Seventeen (60.7%) patients showed loss of methylation of the MEG3/DLK1 intergenic differentially methylated region by epimutation. Eight (28.6%) patients had maternal uniparental disomy of chromosome 14 and three (10.7%) had a paternal deletion in 14q32.2. Most patients (72.7%) had a Netchine-Harbison SRS clinical scoring system ≥4/6, and consistent with a clinical diagnosis of SRS. The mean age at puberty onset was 7.2 years in girls and 9.6 years in boys; 37.5% had premature pubarche. The body mass index of all patients increased before pubarche and/or the onset of puberty. Multilocus analysis identified multiple methylation defects in 58.8% of patients. We identified four potentially damaging genetic variants in genes encoding proteins involved in the establishment or maintenance of DNA methylation. Conclusions - Most patients with 14q32.2 disruption fulfill the criteria for a clinical diagnosis of SRS. These clinical data suggest similar management of patients with TS and SRS, with special attention to their young age at the onset of puberty and early increase of body mass index.

Dates et versions

hal-01926795 , version 1 (19-11-2018)

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Citer

Sophie Geoffron, Walid Abi Habib, Sandra Chantot-Bastaraud, Beatrice Dubern, Virginie Steunou, et al.. Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome. Journal of Clinical Endocrinology and Metabolism, 2018, 103 (7), pp.2436 - 2446. ⟨10.1210/jc.2017-02152⟩. ⟨hal-01926795⟩
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