Titre :

Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

Auteur(s) :

Nassisi, Marco [Auteur]
Université Paris-Sorbonne [UP4]
Institut de la Vision

Mohand-Said, Saddek [Auteur]
Institut de la Vision
DHAENENS, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Boyard, Fiona [Auteur]
Institut de la Vision
Demontant, Vanessa [Auteur]
Institut de la Vision
Andrieu, Camille [Auteur]
Fondation Ophtalmologique Adolphe de Rothschild [Paris]
Antonio, Aline [Auteur]
Institut de la Vision
Condroyer, Christel [Auteur]
Institut de la Vision
Foussard, Marine [Auteur]
Institut de la Vision
Mejecase, Cecile [Auteur]
Institut de la Vision
Eandi, Chiara Maria [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Sahel, Jose-Alain [Auteur]
Institut de la Vision
Zeitz, Christina [Auteur]
Institut de la Vision
Audo, Isabelle [Auteur]
Institut de la Vision

Titre de la revue :

International journal of molecular sciences

Nom court de la revue :

Int J Mol Sci

Numéro :

19

Pagination :

2196

Éditeur :

MDPI

Date de publication :

2018-07-27

ISSN :

1422-0067

Mot(s)-clé(s) :

Stargardt disease
phenotype-genotype correlation
ABCA4

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic ...
Lire la suite >Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt diseaseLire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Alzheimer et Tauopathies

Date de dépôt :

2021-06-23T11:45:29Z
2022-11-16T10:33:03Z