Molecular background of Leber congenital amaurosis in a Polish cohort of patients-novel variants discovered by NGS.
J Appl Genet
; 64(1): 89-104, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36369640
ABSTRACT
Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophies and the most frequent cause of congenital blindness in children. To date, 25 genes have been implicated in the pathogenesis of this rare disorder. Performing an accurate molecular diagnosis is crucial as gene therapy is becoming available. This study aimed to report the molecular basis of Leber congenital amaurosis, especially novel and rare variants in 27 Polish families with a clinical diagnosis of LCA fully confirmed by molecular analyses. Whole exome sequencing or targeted next-generation sequencing (NGS) of inherited retinal dystrophies-associated (IRD) genes was applied to identify potentially pathogenic variants. Bidirectional Sanger sequencing and quantitative PCR (qPCR) were carried out for validation and segregation analysis of the variants identified within the families. We identified 28 potentially pathogenic variants, including 11 novel, in 8 LCA genes CEP290, CRB1, GUCY2D, NMNAT1, RPGRIP1, CRX, LRAT1, and LCA5. This study expands the mutational spectrum of the LCA genes. Moreover, these results, together with the conclusions from our previous studies, allow us to point to the most frequently mutated genes and variants in the Polish cohort of LCA patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Amaurose Congênita de Leber
/
Distrofias Retinianas
/
Nicotinamida-Nucleotídeo Adenililtransferase
Tipo de estudo:
Risk_factors_studies
Limite:
Child
/
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Appl Genet
Assunto da revista:
GENETICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Polônia