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Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome
Author(s) -
Legendre Marine,
Abadie Véronique,
AttiéBitach Tania,
Philip Nicole,
Busa Tiffany,
Bonneau Dominique,
Colin Estelle,
Dollfus Hélène,
Lacombe Didier,
Toutain Annick,
Blesson Sophie,
Julia Sophie,
MartinCoignard Dominique,
Geneviève David,
Leheup Bruno,
Odent Sylvie,
Jouk PierreSimon,
Mercier Sandra,
Faivre Laurence,
VincentDelorme Catherine,
Francannet Christine,
Naudion Sophie,
MathieuDramard Michèle,
Delrue MarieAnge,
Goldenberg Alice,
Héron Delphine,
Parent Philippe,
Touraine Renaud,
Layet Valérie,
Sanlaville Damien,
Quélin Chloé,
Moutton Sébastien,
Fradin Mélanie,
Jacquette Aurélia,
Sigaudy Sabine,
Pinson Lucile,
Sarda Pierre,
Guerrot AnneMarie,
Rossi Massimiliano,
MasurelPaulet Alice,
El Chehadeh Salima,
Piguel Xavier,
RodriguezBallesteros Montserrat,
Ragot Stéphanie,
Lyonnet Stanislas,
Bilan Frédéric,
GilbertDussardier Brigitte
Publication year - 2017
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31591
Subject(s) - charge syndrome , choanal atresia , coloboma , hypoplasia , kallmann syndrome , genotype , biology , microphthalmia , genotype phenotype distinction , genetic testing , anosmia , atresia , medicine , pathology , genetics , anatomy , gene , disease , covid-19 , infectious disease (medical specialty)
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 ([Blake, K. D., 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.