Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants
Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic ERCC8 (CS-A) or ERCC6 (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without pho...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Impact Journals
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320540/ https://www.ncbi.nlm.nih.gov/pubmed/35748794 http://dx.doi.org/10.18632/aging.204139 |
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author | Duong, Nguyen Thuy Dinh, Tran Huu Möhl, Britta S. Hintze, Stefan Quynh, Do Hai Ha, Duong Thi Thu Ngoc, Ngo Diem Dung, Vu Chi Miyake, Noriko Hai, Nong Van Matsumoto, Naomichi Meinke, Peter |
author_facet | Duong, Nguyen Thuy Dinh, Tran Huu Möhl, Britta S. Hintze, Stefan Quynh, Do Hai Ha, Duong Thi Thu Ngoc, Ngo Diem Dung, Vu Chi Miyake, Noriko Hai, Nong Van Matsumoto, Naomichi Meinke, Peter |
author_sort | Duong, Nguyen Thuy |
collection | PubMed |
description | Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic ERCC8 (CS-A) or ERCC6 (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without photosensitivity, which delayed a clinical diagnosis for 16 years. By whole-exome sequencing we identified the two novel compound heterozygous ERCC8 variants c.370_371del (p.L124Efs*15) and c.484G>C (p.G162R). The causality of the ERCC8 variants, of which one results in a frameshift and the other affects the WD3 domain, was tested and confirmed by a rescue experiment investigating DNA repair in H(2)O(2) treated patient fibroblasts. Structural modeling of the p.G162R variant indicates effects on protein-protein interaction. This case shows the importance to test for ERCC6 and ERCC8 variants even if patients do not present with a complete CS phenotype. |
format | Online Article Text |
id | pubmed-9320540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-93205402022-07-27 Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants Duong, Nguyen Thuy Dinh, Tran Huu Möhl, Britta S. Hintze, Stefan Quynh, Do Hai Ha, Duong Thi Thu Ngoc, Ngo Diem Dung, Vu Chi Miyake, Noriko Hai, Nong Van Matsumoto, Naomichi Meinke, Peter Aging (Albany NY) Research Paper Cockayne syndrome (CS) is a rare progeroid disorder characterized by growth failure, microcephaly, photosensitivity, and premature aging, mainly arising from biallelic ERCC8 (CS-A) or ERCC6 (CS-B) variants. In this study we describe siblings suffering from classical Cockayne syndrome but without photosensitivity, which delayed a clinical diagnosis for 16 years. By whole-exome sequencing we identified the two novel compound heterozygous ERCC8 variants c.370_371del (p.L124Efs*15) and c.484G>C (p.G162R). The causality of the ERCC8 variants, of which one results in a frameshift and the other affects the WD3 domain, was tested and confirmed by a rescue experiment investigating DNA repair in H(2)O(2) treated patient fibroblasts. Structural modeling of the p.G162R variant indicates effects on protein-protein interaction. This case shows the importance to test for ERCC6 and ERCC8 variants even if patients do not present with a complete CS phenotype. Impact Journals 2022-06-22 /pmc/articles/PMC9320540/ /pubmed/35748794 http://dx.doi.org/10.18632/aging.204139 Text en Copyright: © 2022 Duong et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Duong, Nguyen Thuy Dinh, Tran Huu Möhl, Britta S. Hintze, Stefan Quynh, Do Hai Ha, Duong Thi Thu Ngoc, Ngo Diem Dung, Vu Chi Miyake, Noriko Hai, Nong Van Matsumoto, Naomichi Meinke, Peter Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title | Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title_full | Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title_fullStr | Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title_full_unstemmed | Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title_short | Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants |
title_sort | cockayne syndrome without uv-sensitivity in vietnamese siblings with novel ercc8 variants |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320540/ https://www.ncbi.nlm.nih.gov/pubmed/35748794 http://dx.doi.org/10.18632/aging.204139 |
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