Screening of potential novel candidate genes in schwannomatosis patients.

Autor: Perez-Becerril C; School of Biological Sciences, Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Wallace AJ; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Schlecht H; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Bowers NL; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Smith PT; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Gokhale C; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Eaton H; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Charlton C; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Robinson R; North East and Yorkshire Genomic Laboratory Hub, St James's University Hospital, Leeds, UK., Charlton RS; North East and Yorkshire Genomic Laboratory Hub, St James's University Hospital, Leeds, UK., Evans DG; School of Biological Sciences, Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Smith MJ; School of Biological Sciences, Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Oct; Vol. 43 (10), pp. 1368-1376. Date of Electronic Publication: 2022 Jun 27.
DOI: 10.1002/humu.24424
Abstrakt: Schwannomatosis comprises a group of hereditary tumor predisposition syndromes characterized by, usually benign, multiple nerve sheath tumors, which frequently cause severe pain that does not typically respond to drug treatments. The most common schwannomatosis-associated gene is NF2, but SMARCB1 and LZTR1 are also associated. There are still many cases in which no pathogenic variants (PVs) have been identified, suggesting the existence of as yet unidentified genetic risk factors. In this study, we performed extended genetic screening of 75 unrelated schwannomatosis patients without identified germline PVs in NF2, LZTR1, or SMARCB1. Screening of the coding region of DGCR8, COQ6, CDKN2A, and CDKN2B was carried out, based on previous reports that point to these genes as potential candidate genes for schwannomatosis. Deletions or duplications in CDKN2A, CDKN2B, and adjacent chromosome 9 region were assessed by multiplex ligation-dependent probe amplification analysis. Sequencing analysis of a patient with multiple schwannomas and melanomas identified a novel duplication in the coding region of CDKN2A, disrupting both p14ARF and p16INK4a. Our results suggest that none of these genes are major contributors to schwannomatosis risk but the possibility remains that they may have a role in more complex mechanisms for tumor predisposition.
(© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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