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Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration
Purpose: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES). Methods: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826738/ https://www.ncbi.nlm.nih.gov/pubmed/31635417 http://dx.doi.org/10.3390/genes10100825 |
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author | Shoshany, Nadav Weiner, Chen Safir, Margarita Einan-Lifshitz, Adi Pokroy, Russell Kol, Ayala Modai, Shira Shomron, Noam Pras, Eran |
author_facet | Shoshany, Nadav Weiner, Chen Safir, Margarita Einan-Lifshitz, Adi Pokroy, Russell Kol, Ayala Modai, Shira Shomron, Noam Pras, Eran |
author_sort | Shoshany, Nadav |
collection | PubMed |
description | Purpose: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES). Methods: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H (CFH) p.Y402H; and age related maculopathy susceptibility 2 (ARMS2) p.A69S; and rare variants complement factor-I (CFI) p.V412M; and hemicentin1 (HMCN1) c.4163delC identified previously in our population. Four families, whose initial screening for the aforementioned variants was negative, underwent WES (phase-2). Bioinformatics filtering was based on functionality (from a panel of 234 genes with proven or presumed association to AMD); predicted severity; and frequency (rare variants with minor allele frequency <1%). When applicable, further screening for specific rare variants was carried out on additional cases of similar ethnicities and phenotypes (phase-3). Results: Phase-1 identified three families carrying CFI p.V412M mutation. WES analysis detected probable disease-related variants in three out of the remaining families. These included: a family with a variant in PLEKHA1 gene p.S177N; a family with previously reported variant p.R1210C in CFH gene; and two families with the C3 p.R735W variant. Conclusions: Rare, high-penetrance variants have a profound contribution to early-AMD pathogenesis. Utilization of WES in genetic research of multifactorial diseases as AMD, allows a thorough comprehensive analysis with the identification of previously unreported rare variants. |
format | Online Article Text |
id | pubmed-6826738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68267382019-11-18 Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration Shoshany, Nadav Weiner, Chen Safir, Margarita Einan-Lifshitz, Adi Pokroy, Russell Kol, Ayala Modai, Shira Shomron, Noam Pras, Eran Genes (Basel) Article Purpose: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES). Methods: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H (CFH) p.Y402H; and age related maculopathy susceptibility 2 (ARMS2) p.A69S; and rare variants complement factor-I (CFI) p.V412M; and hemicentin1 (HMCN1) c.4163delC identified previously in our population. Four families, whose initial screening for the aforementioned variants was negative, underwent WES (phase-2). Bioinformatics filtering was based on functionality (from a panel of 234 genes with proven or presumed association to AMD); predicted severity; and frequency (rare variants with minor allele frequency <1%). When applicable, further screening for specific rare variants was carried out on additional cases of similar ethnicities and phenotypes (phase-3). Results: Phase-1 identified three families carrying CFI p.V412M mutation. WES analysis detected probable disease-related variants in three out of the remaining families. These included: a family with a variant in PLEKHA1 gene p.S177N; a family with previously reported variant p.R1210C in CFH gene; and two families with the C3 p.R735W variant. Conclusions: Rare, high-penetrance variants have a profound contribution to early-AMD pathogenesis. Utilization of WES in genetic research of multifactorial diseases as AMD, allows a thorough comprehensive analysis with the identification of previously unreported rare variants. MDPI 2019-10-18 /pmc/articles/PMC6826738/ /pubmed/31635417 http://dx.doi.org/10.3390/genes10100825 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shoshany, Nadav Weiner, Chen Safir, Margarita Einan-Lifshitz, Adi Pokroy, Russell Kol, Ayala Modai, Shira Shomron, Noam Pras, Eran Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title | Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title_full | Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title_fullStr | Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title_full_unstemmed | Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title_short | Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration |
title_sort | rare genetic variants in jewish patients suffering from age-related macular degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826738/ https://www.ncbi.nlm.nih.gov/pubmed/31635417 http://dx.doi.org/10.3390/genes10100825 |
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