Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis

Miriam Smith, Bertand Isidor, Christian Beetz, Simon Williams, Sanjeev S Bhaskar, Wilfrid Richer, James O'Sullivan, Beverley Anderson, Sarah Daly, Jill Urquhart, Alan Fryer, Cecilie F Rustad, Samantha J Mills, Amir Samii, Daniel du Plessis, Dorothy Halliday, Sebastien Barbarot, Franck Bourdeaut, William Newman, Gareth Evans

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)141-147
Number of pages6
Issue number2
Publication statusPublished - 13 Jan 2015


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