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Research Paper|Volume 14, Issue 13|pp 5299—5310

Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants

Nguyen Thuy Duong1, Tran Huu Dinh1, Britta S. Möhl2, Stefan Hintze3, Do Hai Quynh1, Duong Thi Thu Ha1, Ngo Diem Ngoc4, Vu Chi Dung4, Noriko Miyake5,6, Nong Van Hai1, Naomichi Matsumoto5, Peter Meinke3
  • 1Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
  • 2Institute of Virology, School of Medicine, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany
  • 3Friedrich-Baur-Institute, Department of Neurology, LMU Klinikum, Ludwig-Maximilians-University Munich, Munich, Germany
  • 4Vietnam National Children’s Hospital, Hanoi, Vietnam
  • 5Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
  • 6Department of Human Genetics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
Received: September 24, 2021Accepted: June 14, 2022Published: June 22, 2022
https://doi.org/10.18632/aging.204139

Copyright: © 2022 Duong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 H2O2 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.