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 und Meinke, Peter (2022): Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants. In: Aging, Bd. 14, Nr. 13: S. 5299-5310

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1945-4589
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892