Title :

Prevalence of ABCA4 Deep-Intronic Variants and Related Phenotype in An Unsolved “One-Hit” Cohort with Stargardt Disease

Author(s) :

Nassisi, Marco [Auteur]
Centre d'investigation clinique Quinze-Vingts [CHNO] [CIC1423 - CIC QUINZE-VINGTS]
Mohand-Said, Saddek [Auteur]
Institut de la Vision
Andrieu, Camille [Auteur]
Centre d'investigation clinique Quinze-Vingts [CHNO] [CIC1423 - CIC QUINZE-VINGTS]
Antonio, Aline [Auteur]
Institut de la Vision
Condroyer, Christel [Auteur]
Institut de la Vision
Mejecase, Cecile [Auteur]
Institut de la Vision
Varin, Juliette [Auteur]
Institut de la Vision
Wohlschlegel, Juliette [Auteur]
Institut de la Vision
DHAENENS, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Sahel, Jose-Alain [Auteur]
Centre d'investigation clinique Quinze-Vingts [CHNO] [CIC1423 - CIC QUINZE-VINGTS]
Zeitz, Christina [Auteur]
Institut de la Vision
Audo, Isabelle [Auteur]
Institut de la Vision

Journal title :

International Journal of Molecular Sciences

Abbreviated title :

Int J Mol Sci

Volume number :

20

Pages :

5053

Publication date :

2019-10-11

ISSN :

1422-0067

Keyword(s) :

ABCA4
Stargardt disease
genotype-phenotype correlation
deep-intronic variants

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing ...
Show more >We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G>A in intron 36 (6 subjects), c.4539+2064C>T in intron 30 (4 subjects) and c.4253+43G>A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G>A was mostly associated with a mild phenotype and the c.4539+2064C>T with a more severe one. A variable effect was instead associated with the variant c.4253+43G>A. In addition, two novel variants, c.768+508A>G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients’ selection for clinical trials.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Alzheimer et Tauopathies

Submission date :

2021-06-23T13:44:08Z
2023-01-04T10:47:25Z