Abstract
Sturge–Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary malformation (port-wine stains), and choroidal and leptomeningeal vascular malformations. Previously, the recurrent somatic mutation c.548G>A (p.R183Q) in the G-α q gene (GNAQ) was identified as causative in SWS and non-syndromic port-wine stain patients using whole-genome sequencing. In this study, we investigated somatic mutations in GNAQ by next-generation sequencing. We first performed targeted amplicon sequencing of 15 blood–brain-paired samples in sporadic SWS and identified the recurrent somatic c.548G>A mutation in 80% of patients (12 of 15). The percentage of mutant alleles in brain tissues of these 12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any of the seven GNAQ exons in the remaining three patients without c.548G>A. These findings suggest that the recurrent somatic GNAQ mutation c.548G>A is the major determinant genetic factor for SWS and imply that other mutated candidate gene(s) may exist in SWS.
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Acknowledgements
We thank the patients for participating in this work. We also thank Nobuko Watanabe for technical assistance. This study was supported by the Ministry of Health, Labour and Welfare of Japan, a Grant-in-Aid for Scientific Research (A), (B) and (C) from the Japan Society for the Promotion of Science, the Takeda Science Foundation, the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems, the Strategic Research Program for Brain Sciences and a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Nakashima, M., Miyajima, M., Sugano, H. et al. The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge–Weber syndrome. J Hum Genet 59, 691–693 (2014). https://doi.org/10.1038/jhg.2014.95
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DOI: https://doi.org/10.1038/jhg.2014.95
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