journal contribution
posted on 2023-05-18, 07:09 authored by Michael S Hildebrand, A Simon Harvey, Stephen Malone, John A Damiano, Hongdo Do, Zimeng Ye, Lara McQuillan, Wirginia Maixner, Renate Kalnins, Bernadette Nolan, Martin Wood, Ezgi Ozturk, Nigel C Jones, Greta Gillies, Kate Pope, Paul J Lockhart, Alexander Dobrovic, Richard J Leventer, Ingrid E Scheffer, Samuel F Berkovic Objective: To determine whether the GNAQ R183Q mutation is present in the forme fruste cases of Sturge-Weber syndrome (SWS) to establish a definitive molecular diagnosis. Methods: We used sensitive droplet digital PCR (ddPCR) to detect and quantify the GNAQ mutation in tissues from epilepsy surgery in 4 patients with leptomeningeal angiomatosis; none had ocular or cutaneous manifestations. Results: Low levels of the GNAQ mutation were detected in the brain tissue of all 4 cases - ranging from 0.42% to 7.1% frequency - but not in blood-derived DNA. Molecular evaluation confirmed the diagnosis in 1 case in which the radiologic and pathologic data were equivocal. Conclusions: We detected the mutation at low levels, consistent with mosaicism in the brain or skin (1.0%-18.1%) of classic cases. Our data confirm that the forme fruste is part of the spectrum of SWS, with the same molecular mechanism as the classic disease and that ddPCR is helpful where conventional diagnosis is uncertain.
Funding
This study was supported by the National Health and Medical Research Council Program Grant (1091593) to I.E.S. and S.F.B., a Project Grant (1129054) to S.F.B., a Project Grant (1079058) to M.S.H., a Practitioner Fellowship (1006110) to I.E.S., and a R.D Wright Career Development Fellowship (1063799) to M.S.H. R.J.L. is supported by a Melbourne Children's Clinician Scientist Fellowship.
History
Publication Date
2018-06-01Journal
Neurology GeneticsVolume
4Issue
3Article Number
e236Pagination
5p.Publisher
Wolters Kluwer Health, Inc. on behalf of the American Academy of NeurologyISSN
2376-7839Rights Statement
© 2018 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.