A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth. Academic Article uri icon

Overview

abstract

  • BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCULSIONS: GNA11 mutations are associated with extremity capillary malformations causing overgrowth. Pharmacotherapy that affects GNA11 signaling may prevent the progression of capillary malformations.

publication date

  • January 24, 2017

Research

keywords

  • Capillaries
  • Extremities
  • GTP-Binding Protein alpha Subunits
  • Mutation
  • Vascular Malformations

Identity

PubMed Central ID

  • PMC5511772

Scopus Document Identifier

  • 85010735062

Digital Object Identifier (DOI)

  • 10.1007/s10456-016-9538-1

PubMed ID

  • 28120216

Additional Document Info

volume

  • 20

issue

  • 3