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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
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.
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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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