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Article Dans Une Revue American Journal of Medical Genetics Part C: Seminars in Medical Genetics Année : 2017

Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome

1 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
2 Service de génétique clinique [Poitiers]
3 Neuvacod - Unité neurovasculaire et troubles cognitifs
4 SMSP - U1178 - Santé mentale et santé publique
5 Hôpital Necker - Enfants Malades [AP-HP]
6 Service de Génétique Médicale [CHU Necker]
7 Equipe Inserm U1163 - Embryology and genetics of human malformation
8 GMGF - Génétique Médicale et Génomique Fonctionnelle
9 Département de génétique médicale [Hôpital de la Timone - APHM]
10 MITOVASC - MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale
11 Service de génétique [Angers]
12 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
13 Service de génétique médicale
14 U1211 INSERM/MRGM - Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux)
15 Service de génétique [Tours]
16 LEASP - Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps
17 Centre Hospitalier Le Mans (CH Le Mans)
18 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
19 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
20 Service de Génétique [CHRU Nancy]
21 Service de génétique clinique [Rennes]
22 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
23 Service de génétique médicale - Unité de génétique clinique [Nantes]
24 GAD - Génétique des Anomalies du Développement
25 Service de Génétique Médicale [Lille]
26 Service de Génétique Médicale [CHU Clermont-Ferrand]
27 Unité de génétique médicale et oncogénétique [CHU Amiens Picardie]
28 Service de génétique [Rouen]
29 Institut de Myologie
30 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
31 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
32 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
33 Service de génétique médicale [Montpellier]
34 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
35 Service de Cardiologie (hôpital général, CHU Dijon)
36 Service Endocrinologie [CHU Poitiers]
37 Service Génétique Médicale [CHU Poitiers]
Annick Toutain
Laurence Faivre
  • Fonction : Auteur
  • PersonId : 856301
Valérie Layet
  • Fonction : Auteur

Résumé

CHARGE syndrome (CS) is a genetic disorder whose first description included Coloboma, Heart disease, Atresia of choanae, Retarded growth and development, Genital hypoplasia, and Ear anomalies and deafness, most often caused by a genetic mutation in the CHD7 gene. Two features were then added: semicircular canal anomalies and arhinencephaly/olfactory bulb agenesis, with classification of typical, partial, or atypical forms on the basis of major and minor clinical criteria. The detection rate of a pathogenic variant in the CHD7 gene varies from 67% to 90%. To try to have an overview of this heterogenous clinical condition and specify a genotype-phenotype relation, we conducted a national study of phenotype and genotype in 119 patients with CS. Selected clinical diagnostic criteria were from Verloes (2005), updated by Blake & Prasad (2006). Besides obtaining a detailed clinical description, when possible, patients underwent a full ophthalmologic examination, audiometry, temporal bone CT scan, gonadotropin analysis, and olfactory-bulb MRI. All patients underwent CHD7 sequencing and MLPA analysis. We found a pathogenic CHD7 variant in 83% of typical CS cases and 58% of atypical cases. Pathogenic variants in the CHD7 gene were classified by the expected impact on the protein. In all, 90% of patients had a typical form of CS and 10% an atypical form. The most frequent features were deafness/semicircular canal hypoplasia (94%), pituitary defect/hypogonadism (89%), external ear anomalies (87%), square-shaped face (81%), and arhinencephaly/anosmia (80%). Coloboma (73%), heart defects (65%), and choanal atresia (43%) were less frequent.
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Dates et versions

hal-01691932 , version 1 (04-05-2018)

Identifiants

Citer

Marine Legendre, Véronique Abadie, Tania Attié-Bitach, Nicole Philip, Tiffany Busa, et al.. Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2017, 175 (4), pp.417 - 430. ⟨10.1002/ajmg.c.31591⟩. ⟨hal-01691932⟩
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