The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge-Weber syndrome.
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.
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Mitsuko
M
Nakashima
Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Masakazu
M
Miyajima
Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Hidenori
H
Sugano
Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Yasushi
Y
Iimura
Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
Mitsuhiro
M
Kato
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yoshinori
Y
Tsurusaki
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Noriko
N
Miyake
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Hirotomo
H
Saitsu
Department of Neurosurgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Hajime
H
Arai
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Naomichi
N
Matsumoto
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D019339:Port-Wine Stain / Q000235:genetics* / Q000503:physiopathology; D013341:Sturge-Weber Syndrome / Q000235:genetics* / Q000503:physiopathology
C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11