Genetic Spectrum of ABCA4-Associated Retinal Degeneration in Poland
Publication year
2019Source
Genes, 10, 12, (2019), article E959ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Internal Medicine
Journal title
Genes
Volume
vol. 10
Issue
iss. 12
Subject
Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical NeuroscienceAbstract
Mutations in retina-specific ATP-binding cassette transporter 4 (ABCA4) are responsible for over 95% of cases of Stargardt disease (STGD), as well as a minor proportion of retinitis pigmentosa (RP) and cone-rod dystrophy cases (CRD). Since the knowledge of the genetic causes of inherited retinal diseases (IRDs) in Poland is still scarce, the purpose of this study was to identify pathogenic ABCA4 variants in a subgroup of Polish IRD patients. We recruited 67 families with IRDs as a part of a larger study. The patients were screened with next generation sequencing using a molecular inversion probes (MIPs)-based technique targeting 108 genes involved in the pathogenesis of IRDs. All identified mutations were validated and their familial segregation was tested using Sanger sequencing. In the case of the most frequent complex allele, consisting of two variants in exon 12 and 21, familial segregation was tested using restriction fragment length polymorphism (RFLP). The most prevalent variant, a complex change c.[1622T>C;3113C>T], p.[Leu541Pro;Ala1038Val], was found in this cohort in 54% of all solved ABCA4-associated disorder cases, which is the highest frequency reported thus far. Additionally, we identified nine families displaying a pseudo-dominant mode of inheritance, indicating a high frequency of pathogenic variants within this population.
This item appears in the following Collection(s)
- Academic publications [203856]
- Electronic publications [102283]
- Faculty of Medical Sciences [80326]
- Open Access publications [70938]
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