Novel mutations in Polish patients with hereditary retinal disorders

Abstract

Purpose : The knowledge about the genetic causes of hereditary retinal disorders (HRDs) in Polish population is still scarce and patients suffering from these diseases commonly lack genetic diagnostics and counselling. Our project aims to investigate mutation spectrum in known HRD genes in Polish families with retinitis pigmentosa, Leber congenital amaurosis, Stargardt’s disease, cone- and cone-rod dystrophy, congenital stationary night blindness and achromatopsia.

Methods : Hitherto, we collected DNA samples from affected and healthy individuals from 40 Polish families suffering from HRD. Next generation sequencing was performed using molecular inversion probes pool targeting 108 HRD genes known in 2013. Subsequently, we analyzed the samples using bioinformatic software suite: SeqPilot (module SeqNext) using most stringent settings allowing for detection of highest quality truncating, non-synonymous and splice site variants. We applied filtering for known variants occurring with frequency >0,5% in public databases. In case of novel missense or splicing mutations, we applied in-silico prediction software to assess mutation causality.

Results : We detected causative mutations in 20 of the 40 HRD families. 9 novel mutations were identified in ABCA4, CEP290, CRB1, PRPF8, MFRP, MERTK and TOPORS and 17 previously known mutated alleles were detected. Five Stargardt disease patients carried single ABCA4 causative allele.

Conclusions : Our results so far confirm the hypothesis that Polish population bears many different alterations than the ones in Western Europe. Therefore, microarray chips with known mutations based on Western populations, which have hitherto been commonly used for diagnostics, may not be optimal for use in Polish patients. More than half of the identified mutations is novel, therefore it is justified to conclude that they may be unique for the Polish population.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.