July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Next generation sequencing using molecular inversion probes in hereditary retinal disorders genes in Polish patients: an update
Author Affiliations & Notes
  • Anna M. Tracewska-Siemiatkowska
    DNA Analysis Laboratory, PORT Polish Center for Technology Development, 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
  • Agnieszka Rafalska
    Department of Ophthalmology, Wroclaw Medical University, Wroclaw, Poland
  • Malgorzata Rydzanicz
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Wallis and Futuna
  • Piotr Stawinski
    Department of Medical Genetics, Medical University of Warsaw, Warsaw, Wallis and Futuna
  • Elzbieta Ciara
    Children's Memorial Health Institute, 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
  • Arjen Henkes
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
  • Alexander Hoischen
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
  • Christian Gilisen
    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 der Vorst
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
    Donders Institute for Brain, Cognition and Behavior, 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, Wallis and Futuna
  • 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; Agnieszka Rafalska, None; Malgorzata Rydzanicz, None; Piotr Stawinski, None; Elzbieta Ciara, None; Muhammad Imran Khan, None; Arjen Henkes, None; Alexander Hoischen, None; Christian Gilisen, None; Maartje van der Vorst, None; Frans Cremers, None; Rafal Ploski, None; Krystyna Chrzanowska, None
  • Footnotes
    Support  National Science Centre, grant no. 015/19/D/NZ2/03193
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2941. doi:
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      Anna M. Tracewska-Siemiatkowska, Joanna Murawska, Beata Kocyla-Karczmarewicz, Marek Szalinski, Agnieszka Rafalska, Malgorzata Rydzanicz, Piotr Stawinski, Elzbieta Ciara, Muhammad Imran Khan, Arjen Henkes, Alexander Hoischen, Christian Gilisen, Maartje van der Vorst, Frans P Cremers, Rafal Ploski, Krystyna Chrzanowska; Next generation sequencing using molecular inversion probes in hereditary retinal disorders genes in Polish patients: an update. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2941.

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

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Abstract

Purpose : The knowledge of mutational spectrum in hereditary retinal disorders (HRDs) within Polish population is still limited. Our ongoing project targets known HRD genes in Polish families with Stargardt’s disease, retinitis pigmentosa, choroideremia, cone- and cone-rod dystrophy, achromatopsia and congenital stationary night blindness. The purpose is to gain knowledge about the type and prevalence of causative variants. Hitherto, we provide an update on this research.

Methods : We collected DNA samples from 208 Polish families suffering from HRD. One family withdrew from the project. Thus far, 162 probands underwent next generation sequencing. A molecular inversion probes pool was used, which targeted 108 HRD genes known in 2013. Subsequently, we analyzed the samples with the use of SeqNext module of SeqPilot software. We then applied filtering for known variants occurring with frequency >0,5% in public databases, with the exception of ABCA4 mutations, when the frequency filter was set to 3%. In case of novel missense or splicing mutations, we applied in-silico prediction software to assess mutation causality.

Results : We detected potentially causative mutations in116 of the 162 HRD families (71%); 60 individuals with STGD, RP and CD/CRD carried ABCA4 mutations (4 single-allelic). On top of previously reported 9 novel mutations from this study, additional novel variants were found in ABCA4, RHO, MAK and CNGA3. The complex allele [c.1622T>C,c.3113C>T] [p.Leu541Pro,p.Ala1038Val] was found in 33 individuals suffering from ABCA4-related disorders, which makes it the most prevalent allele in Polish population (55%). In one case, after genetic screening, the diagnosis changed from RP to choroideremia, which may have impact on future gene therapy in this family.

Conclusions : Our results indicate that ABCA4 mutations are the most common cause of HRDs in Poland. Therefore, it should be the first gene to be analysed. Additionally, it needs to be stressed that in some cases genetic analysis of the patient is necessary to achieve accurate diagnosis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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