Screening of potential novel candidate genes in schwannomatosis patients

• DOI: 10.1002/humu.24424
• Publication Date: 2022-06-20T14:33:49Z
• Authors: Cristina Perez‐Be...; Andrew J. Wallace; Helene Schlecht; Naomi L. Bowers; Philip T. Smith; Carolyn Gokhale; Helen Eaton; Chris Charlton; Rachel Robinson; Ruth S. Charlton; D. Gareth Evans; Miriam J. Smith
• Keywords: CDKN2B; SMARCB1; Candidate gene; Neurofibromatosis type 2

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 still many cases in no pathogenic variants (PVs) have been identified, suggesting the existence as yet unidentified genetic risk factors. In this study, we performed extended screening 75 unrelated schwannomatosis patients without identified germline PVs LZTR1, or SMARCB1. Screening coding region DGCR8, COQ6, CDKN2A, CDKN2B was carried out, based on previous reports point these genes potential candidate for schwannomatosis. Deletions duplications CDKN2B, adjacent chromosome 9 were assessed by multiplex ligation-dependent probe amplification analysis. Sequencing analysis patient with schwannomas melanomas novel duplication disrupting both p14ARF p16INK4a. Our results suggest none major contributors possibility remains they may role more complex mechanisms predisposition.