Whole-Exome Analysis for Polish Caucasian Patients with Retinal Dystrophies and the Creation of a Reference Genomic Database for the Polish Population

Author:

Matczyńska Ewa12ORCID,Szymańczak Robert1,Stradomska Katarzyna1,Łyszkiewicz Przemysław1,Jędrzejowska Maria1,Kamińska Karolina1ORCID,Beć-Gajowniczek Marta1,Suchecka Ewa1,Zagulski Marek1,Wiącek Marta3ORCID,Wylęgała Edward2ORCID,Machalińska Anna3,Mossakowska Małgorzata4ORCID,Puzianowska-Kuźnicka Monika56ORCID,Teper Sławomir27ORCID,Boguszewska-Chachulska Anna1ORCID

Affiliation:

1. Genomed S.A., 02-971 Warsaw, Poland

2. Chair and Clinical Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland

3. First Department of Ophthalmology, Pomeranian Medical University, 70-204 Szczecin, Poland

4. Study on Ageing and Longevity, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland

5. Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland

6. Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, 01-813 Warsaw, Poland

7. Department of Scientific Research, Branch in Bielsko-Biala, Medical University of Silesia, 43-300 Bielsko-Biała, Poland

Abstract

We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016–2019. Moreover, to facilitate such diagnostic analyses and enable future application of gene therapy and genome editing for IRD patients, a Polish genomic reference database (POLGENOM) was created based on whole-genome sequences of healthy Polish Caucasian nonagenarians and centenarians. The newly constructed database served as a control, providing a comparison for variant frequencies in the Polish population. The diagnostic yield for the selected group of IRD patients reached 64.9%. The study uncovered the most common pathogenic variants in ABCA4 and USH2A in the European population, along with several novel causative variants. A significant frequency of the ABCA4 complex haplotype p.(Leu541Pro; Ala1038Val) was observed, as well as that of the p.Gly1961Glu variant. The first VCAN causative variant NM_004385.5:c.4004-2A>G in Poland was found and described. Moreover, one of the first patients with the RPE65 causative variants was identified, and, in consequence, could receive the dedicated gene therapy. The availability of the reference POLGENOM database enabled comprehensive variant characterisation during the NGS data analysis, confirming the utility of a population-specific genomic database for enhancing diagnostic accuracy. Study findings suggest the significance of genetic testing in elder patients with unclear aetiology of eye diseases. The combined approach of NGS and the reference genomic database can improve the diagnosis, management, and future treatment of IRDs.

Funder

National Centre for Research and Development

Ministry of Science and Higher Education

Publisher

MDPI AG

Reference59 articles.

1. RetNet (2024, April 02). The Retinal Information Network. Available online: https://web.sph.uth.edu/RetNet/.

2. Non-syndromic retinitis pigmentosa;Verbakel;Prog. Retin. Eye Res.,2018

3. Epidemiology of retinitis pigmentosa in Denmark;Haim;Acta Ophthalmol. Scand.,2002

4. Prevalence of RPGR-Mediated Retinal Dystrophy in an Unselected Cohort of Over 5000 Patients;Tuupanen;Transl. Vis. Sci. Technol.,2022

5. Zeviani, M., and Carelli, V. (2021). Mitochondrial Retinopathies. Int. J. Mol. Sci., 23.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3