July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Novel mutations in Polish patients with hereditary retinal disorders
Author Affiliations & Notes
  • Anna Maria Tracewska-Siemiatkowska
    DNA Analysis Laboratory, Wroclaw Research Centre EIT+, Wroclaw, Poland
  • Joanna Murawska
    Department of Ophthalmology, University Clinical Centre, Gdansk, Poland
  • Beata Kocyla-Karczmarewicz
    Children's Memorial Health Institute, Warsaw, Poland
  • Marek Szalinski
    Department of Ophthalmology, Wroclaw Medical University, Wroclaw, Poland
  • Malgorzata Rydzanicz
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
  • Piotr Stawinski
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
  • Muhammad Imran Khan
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
  • Alexander Hoischen
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
  • Christian Gilissen
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
  • Maartje van de Vorst
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
  • Frans P Cremers
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
  • Rafal Ploski
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
  • Krystyna Chrzanowska
    Children's Memorial Health Institute, Warsaw, Poland
  • Footnotes
    Commercial Relationships   Anna Tracewska-Siemiatkowska, None; Joanna Murawska, None; Beata Kocyla-Karczmarewicz, None; Marek Szalinski, None; Malgorzata Rydzanicz, None; Piotr Stawinski, None; Muhammad Khan, None; Alexander Hoischen, None; Christian Gilissen, None; Maartje van de Vorst, None; Frans Cremers, None; Rafal Ploski, None; Krystyna Chrzanowska, None
  • Footnotes
    Support  National Centre of Science (NCN) Grant 2015/19/D/NZ2/03193
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2324. doi:
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      Anna Maria Tracewska-Siemiatkowska, Joanna Murawska, Beata Kocyla-Karczmarewicz, Marek Szalinski, Malgorzata Rydzanicz, Piotr Stawinski, Muhammad Imran Khan, Alexander Hoischen, Christian Gilissen, Maartje van de Vorst, Frans P Cremers, Rafal Ploski, Krystyna Chrzanowska; Novel mutations in Polish patients with hereditary retinal disorders. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2324.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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