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Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population
A substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989631/ https://www.ncbi.nlm.nih.gov/pubmed/31996704 http://dx.doi.org/10.1038/s41598-020-58101-8 |
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author | Lee, Youngha Park, Soojin Lee, Jin Sook Kim, Soo Yeon Cho, Jaeso Yoo, Yongjin Lee, Sangmoon Yoo, Taekyeong Lee, Moses Seo, Jieun Lee, Jeongeun Kneissl, Jana Lee, Jean Jeon, Hyoungseok Jeon, Eun Young Hong, Sung Eun Kim, Eunha Kim, Hyuna Kim, Woo Joong Kim, Jon Soo Ko, Jung Min Cho, Anna Lim, Byung Chan Kim, Won Seop Choi, Murim Chae, Jong-Hee |
author_facet | Lee, Youngha Park, Soojin Lee, Jin Sook Kim, Soo Yeon Cho, Jaeso Yoo, Yongjin Lee, Sangmoon Yoo, Taekyeong Lee, Moses Seo, Jieun Lee, Jeongeun Kneissl, Jana Lee, Jean Jeon, Hyoungseok Jeon, Eun Young Hong, Sung Eun Kim, Eunha Kim, Hyuna Kim, Woo Joong Kim, Jon Soo Ko, Jung Min Cho, Anna Lim, Byung Chan Kim, Won Seop Choi, Murim Chae, Jong-Hee |
author_sort | Lee, Youngha |
collection | PubMed |
description | A substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contribution of recessive variants to Mendelian diseases is still lacking. Therefore, genetic diagnosis and variant discovery of 553 undiagnosed Korean patients with complex neurodevelopmental problems (KND for Korean NeuroDevelopmental cohort) were performed using whole exome sequencing of patients and their parents. Disease-causing variants, including newly discovered variants, were identified in 57.5% of the probands of the KND cohort. Among the patients with the previous reported pathogenic variants, 35.1% inherited these variants in a recessive manner. Genes that cause recessive disorders in our cohort tend to be less constrained by loss-of-function variants and were enriched in lipid metabolism and mitochondrial functions. This observation was applied to an estimation that approximately 1 in 17 healthy Korean individuals carry at least one of these pathogenic variants that develop severe neurodevelopmental problems in a recessive manner. Furthermore, the feasibility of these genes for carrier screening was evaluated. Our results will serve as a foundation for recessive variant screening to reduce occurrences of rare Mendelian disease patients. Additionally, our results highlight the utility and necessity of whole exome sequencing-based diagnostics for improving patient care in a country with a centralized medical system. |
format | Online Article Text |
id | pubmed-6989631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69896312020-02-05 Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population Lee, Youngha Park, Soojin Lee, Jin Sook Kim, Soo Yeon Cho, Jaeso Yoo, Yongjin Lee, Sangmoon Yoo, Taekyeong Lee, Moses Seo, Jieun Lee, Jeongeun Kneissl, Jana Lee, Jean Jeon, Hyoungseok Jeon, Eun Young Hong, Sung Eun Kim, Eunha Kim, Hyuna Kim, Woo Joong Kim, Jon Soo Ko, Jung Min Cho, Anna Lim, Byung Chan Kim, Won Seop Choi, Murim Chae, Jong-Hee Sci Rep Article A substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contribution of recessive variants to Mendelian diseases is still lacking. Therefore, genetic diagnosis and variant discovery of 553 undiagnosed Korean patients with complex neurodevelopmental problems (KND for Korean NeuroDevelopmental cohort) were performed using whole exome sequencing of patients and their parents. Disease-causing variants, including newly discovered variants, were identified in 57.5% of the probands of the KND cohort. Among the patients with the previous reported pathogenic variants, 35.1% inherited these variants in a recessive manner. Genes that cause recessive disorders in our cohort tend to be less constrained by loss-of-function variants and were enriched in lipid metabolism and mitochondrial functions. This observation was applied to an estimation that approximately 1 in 17 healthy Korean individuals carry at least one of these pathogenic variants that develop severe neurodevelopmental problems in a recessive manner. Furthermore, the feasibility of these genes for carrier screening was evaluated. Our results will serve as a foundation for recessive variant screening to reduce occurrences of rare Mendelian disease patients. Additionally, our results highlight the utility and necessity of whole exome sequencing-based diagnostics for improving patient care in a country with a centralized medical system. Nature Publishing Group UK 2020-01-29 /pmc/articles/PMC6989631/ /pubmed/31996704 http://dx.doi.org/10.1038/s41598-020-58101-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lee, Youngha Park, Soojin Lee, Jin Sook Kim, Soo Yeon Cho, Jaeso Yoo, Yongjin Lee, Sangmoon Yoo, Taekyeong Lee, Moses Seo, Jieun Lee, Jeongeun Kneissl, Jana Lee, Jean Jeon, Hyoungseok Jeon, Eun Young Hong, Sung Eun Kim, Eunha Kim, Hyuna Kim, Woo Joong Kim, Jon Soo Ko, Jung Min Cho, Anna Lim, Byung Chan Kim, Won Seop Choi, Murim Chae, Jong-Hee Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title | Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title_full | Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title_fullStr | Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title_full_unstemmed | Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title_short | Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
title_sort | genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989631/ https://www.ncbi.nlm.nih.gov/pubmed/31996704 http://dx.doi.org/10.1038/s41598-020-58101-8 |
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