Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis
| Autor: | Sarah B. Daly, Beverly Anderson, Simon G. Williams, James O'Sullivan, Wilfrid Richer, Miriam J. Smith, William G. Newman, Sanjeev S. Bhaskar, Daniel du Plessis, Amir Samii, Jill E. Urquhart, Christian Beetz, Samantha J Mills, Bertand Isidor, Cecilie F. Rustad, Dorothy Halliday, Sébastien Barbarot, Alan Fryer, D. Gareth Evans, Franck Bourdeaut |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Skin Neoplasms Neurofibromatoses Copy number analysis Loss of Heterozygosity Biology Article Germline Loss of heterozygosity symbols.namesake Germline mutation otorhinolaryngologic diseases medicine Humans Genetic Predisposition to Disease Schwannomatosis Germ-Line Mutation Exome sequencing Sanger sequencing Genetics Neuroma Acoustic Sequence Analysis DNA medicine.disease Pedigree Mutation (genetic algorithm) symbols Female Neurology (clinical) Neurilemmoma Transcription Factors |
| Zdroj: | Neurology. 84:141-147 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000001129 |
| Popis: | Objectives: We aimed to determine the proportion of individuals in our schwannomatosis cohort whose disease is associated with an LZTR1 mutation. Methods: We used exome sequencing, Sanger sequencing, and copy number analysis to screen 65 unrelated individuals with schwannomatosis who were negative for a germline NF2 or SMARCB1 mutation. We also screened samples from 39 patients with a unilateral vestibular schwannoma (UVS), plus at least one other schwannoma, but who did not have an identifiable germline or mosaic NF2 mutation. Results: We identified germline LZTR1 mutations in 6 of 16 patients (37.5%) with schwannomatosis who had at least one affected relative, 11 of 49 (22%) sporadic patients, and 2 of 39 patients with UVS in our cohort. Three germline mutation–positive patients in total had developed a UVS. Mosaicism was excluded in 3 patients without germline mutation in NF2 , SMARCB1 , or LZTR1 by mutation screening in 2 tumors from each. Conclusions: Our data confirm the relationship between mutations in LZTR1 and schwannomatosis. They indicate that germline mutations in LZTR1 confer an increased risk of vestibular schwannoma, providing further overlap with NF2, and that further causative genes for schwannomatosis remain to be identified. |
| Databáze: | OpenAIRE |
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