Format

Send to

Choose Destination
Angiogenesis. 2017 Aug;20(3):303-306. doi: 10.1007/s10456-016-9538-1. Epub 2017 Jan 24.

A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth.

Author information

1
Department of Plastic and Oral Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Orthopedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
3
Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
4
Department of Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
5
Department of Surgery, Vascular Biology Program, Boston Children's Hospital, Boston, MA, USA.
6
Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
7
Department of Plastic and Oral Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. arin.greene@childrens.harvard.edu.

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.

KEYWORDS:

Capillary malformation; Extremity; GNA11; GNAQ; Vascular anomaly

PMID:
28120216
PMCID:
PMC5511772
DOI:
10.1007/s10456-016-9538-1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center