A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth
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Capillary malformation is a cutaneous vascular anomaly that is present at birth, darkens over time, and can cause overgrowth of tissues beneath the stain. The lesion is caused by a somatic activating mutation in GNAQ. In a previous study, we were unable to identify a GNAQ mutation in patients with a capillary malformation involving an overgrown lower extremity. We hypothesized that mutations in GNA11 or GNA14, genes closely related to GNAQ, also may cause capillary malformations.
Human capillary malformation tissue obtained from 8 patients that had tested negative for GNAQ mutations were studied. Lesions involved an extremity (n = 7) or trunk (n = 1). Droplet digital PCR (ddPCR) was used to detect GNA11 or GNA14 mutant cells (p.Arg183) in the specimens. Single molecule molecular inversion probe sequencing (smMIP-seq) was performed to search for other mutations in GNA11. Mutations were validated by subcloning and sequencing amplimers.
We found a somatic GNA11 missense mutation (c.547C > T; p.Arg183Cys) in 3 patients with a diffuse capillary malformation of an extremity. Mutant allelic frequencies ranged from 0.3 to 5.0%. GNA11 or GNA14 mutations were not found in 5 affected tissues or in unaffected tissues (white blood cell DNA).
GNA11 mutations are associated with extremity capillary malformations causing overgrowth. Pharmacotherapy that affects GNA11 signaling may prevent the progression of capillary malformations.
KeywordsCapillary malformation GNAQ GNA11 Vascular anomaly Extremity
Research reported in this manuscript was supported by the National Institutes of Health Award NICHD-81004 (AKG), National Institutes of Health Award NICHD-82606 (AKG), National Institutes of Health Award HL12703 (JB, AKG), National Institutes of Health Award AR-64231 (MLW), the Translational Research Program Mid-Career Award Boston Children’s Hospital (AKG), and the Translational Neuroscience Center Pilot Study Award Boston Children’s Hospital (JB, AKG). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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The authors have no disclosures.
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