Genetic Variants Associated with Port-Wine Stains.
PLoS One
; 10(7): e0133158, 2015.
Article
in En
| MEDLINE
| ID: mdl-26192947
ABSTRACT
BACKGROUND:
Port-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development.OBJECTIVES:
Understanding PWS genetic determinants could provide insight into new treatments.METHODS:
Our study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism.RESULTS:
A novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious.CONCLUSIONS:
This is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Port-Wine Stain
/
P120 GTPase Activating Protein
/
GTP-Binding Protein alpha Subunits
Type of study:
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2015
Document type:
Article
Affiliation country:
Estados Unidos