Non-syndromic inherited retinal diseases in Poland: Genes, mutations, and phenotypes

• Published in: Molecular vision Vol. 27; pp. 457 - 465
• Main Authors: Tracewska, Anna M, Kocyła-Karczmarewicz, Beata, Rafalska, Agnieszka, Murawska, Joanna, Jakubaszko-Jabłónska, Joanna, Rydzanicz, Małgorzata, Stawiński, Piotr, Ciara, Elżbieta, Lipska-Ziętkiewicz, Beata S, Khan, Muhammad Imran, Cremers, Frans P M, Płoski, Rafał, Chrzanowska, Krystyna H
• Format: Journal Article
• Language: English
• Published: United States Molecular Vision 2021
• Subjects: Adolescent; Adult; Aged; Alleles; Blindness; Child; Child, Preschool; Color blindness; Diagnosis; Dystrophy; Eye Diseases, Hereditary - epidemiology; Eye Diseases, Hereditary - genetics; Female; Gene frequency; Genes - genetics; Genetic analysis; Genetic Testing; Genetic Variation; Heredity; Humans; Infant; Male; Middle Aged; Mutation; Mutation - genetics; Next-generation sequencing; Nyctalopia; Patients; Phenotype; Phenotypes; Poland - epidemiology; Population; Population genetics; Population studies; Prevalence; Retina; Retinal Diseases - epidemiology; Retinal Diseases - genetics; Retinitis; Retinitis pigmentosa; Stationary night blindness; Poland
• ISSN: 1090-0535; 1090-0535

Inherited retinal diseases (IRDs), encompassing many clinical entities affecting the retina, are classified as rare disorders. Their extreme heterogeneity made molecular screening in the era before next-generation sequencing (NGS) expensive and time-consuming. Since then, many NGS studies of IRD molecular background have been conducted in Western populations; however, knowledge of the IRD mutational spectrum in Poland is still limited. Until now, there has been almost no comprehensive analysis of this particular population regarding the molecular basis and inheritance of IRDs. Therefore, the purpose of this study was to gain knowledge about the type and prevalence of causative variants in the Polish population. We recruited 190 Polish families with non-syndromic IRDs, including Stargardt disease (STGD), retinitis pigmentosa (RP), cone- and cone-rod dystrophy (CD/CRD), achromatopsia, and congenital stationary night blindness. A pool of molecular inversion probes was used, which targeted 108 genes associated with non-syndromic IRDs known in 2013. We applied filtering for known variants occurring with an allele frequency >0.5% in public and in-house databases, with the exception of variants in , when the frequency filter was set to 3.0%. Hypomorphic p.(Asn1868Ile) was added manually. In the case of novel missense or splicing variants, we used in silico prediction software to assess mutation causality. We detected causative mutations in 115 of the 190 families with non-syndromic IRD (60.2%). Fifty-nine individuals with STGD, RP, and CD/CRD carried causal variants in . Novel single nucleotide variants were found in and . The complex allele c.[1622T>C;3113C>T], p.[Leu541Pro;Ala1038Val] was found in 33 individuals with -associated disorders, which makes it the most prevalent allele in the Polish population (17% of all solved cases). Diagnosis was reevaluated in 16 cases. Previously, there were no comprehensive reports of IRDs in the Polish population. This study is the first to indicate that the most common IRDs in Poland are -associated diseases, regardless of the phenotype. In Polish patients with RP, the second most prevalent causal gene was and the third , while there were not as many mutations in as in Western populations. The number of initial erroneous diagnoses may be the result of limited access to diagnostics with advanced tools, such as electroretinography; however, it is necessary to raise awareness among Polish ophthalmologists of rare IRDs. Additionally, it must be emphasized that in some cases genetic analysis of the patient is necessary to achieve an accurate diagnosis.