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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2020

Open Access 01-12-2020 | Nystagmus | Research

Novel gene variants in Polish patients with Leber congenital amaurosis (LCA)

Authors: Anna Skorczyk-Werner, Zuzanna Niedziela, Marcin Stopa, Maciej Robert Krawczyński

Published in: Orphanet Journal of Rare Diseases | Issue 1/2020

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Abstract

Background

Leber congenital amaurosis (LCA) is a rare retinal disease that is the most frequent cause of congenital blindness in children and the most severe form of inherited retinal dystrophies. To date, 25 genes have been implicated in the pathogenesis of LCA. As gene therapy is becoming available, the identification of potential treatment candidates is crucial. The aim of the study was to report the molecular basis of Leber congenital amaurosis in 22 Polish families.

Methods

Single Nucleotide Polymorphism-microarray for LCA genes or Next Generation Sequencing diagnostic panel for LCA genes (or both tests) were performed to identify potentially pathogenic variants. Bidirectional Sanger sequencing was carried out for validation and segregation analysis of the variants identified within the families.

Results

The molecular background was established in 22 families. From a total of 24 identified variants, 23 were predicted to affect protein-coding or splicing, including 10 novel variants. The variants were identified in 7 genes: CEP290, GUCY2D, RPE65, NMNAT1, CRB1, RPGRIP1, and CRX. More than one-third of the patients, with clinical LCA diagnosis confirmed by the results of molecular analysis, appeared to be affected with a severe form of the disease: LCA10 caused by the CEP290 gene variants. Intronic mutation c.2991+1655A>G in the CEP290 gene was the most frequent variant identified in the studied group.

Conclusions

This study provides the first molecular genetic characteristics of patients with Leber congenital amaurosis from the previously unexplored Polish population. Our study expands the mutational spectrum as we report 10 novel variants identified in LCA genes. The fact that the most frequent causes of the disease in the studied group of Polish patients are mutations in one out of three genes that are currently the targets for gene therapy (CEP290, GUCY2D, and RPE65) strongly emphasizes the importance of the molecular background analyses of LCA in Polish patients.
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Metadata
Title
Novel gene variants in Polish patients with Leber congenital amaurosis (LCA)
Authors
Anna Skorczyk-Werner
Zuzanna Niedziela
Marcin Stopa
Maciej Robert Krawczyński
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Nystagmus
Published in
Orphanet Journal of Rare Diseases / Issue 1/2020
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-020-01634-y

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