Expanding the Clinical and Molecular Findings in RASA1 Capillary Malformation-arteriovenous Malformation

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2018 Jun 13

PMID 29891884

Citations 24

Authors

Whitney L Wooderchak-Donahue

Peter Johnson

Jamie McDonald

Francine Blei

Alejandro Berenstein

Michelle Sorscher

Jennifer Mayer

Angela E Scheuerle

Tracey Lewis

J Fredrik Grimmer

Gresham T Richter

Marcie A Steeves

Angela E Lin

David A Stevenson

Pinar Bayrak-Toydemir

Affiliations

Soon will be listed here.

Abstract

RASA1-related disorders are vascular malformation syndromes characterized by hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. The number of cases reported is relatively small; and while the main clinical features are CMs and AVMs/AVFs, the broader phenotypic spectrum caused by variants in the RASA1 gene is still being defined. Here, we report the clinical and molecular findings in 69 unrelated cases with a RASA1 variant identified at ARUP Laboratories. Sanger sequencing and multiplex ligation-dependent probe amplification were primarily used to evaluate RASA1. Several atypical cases were evaluated using next-generation sequencing (NGS) and array-comparative genomic hybridization (aCGH). Sixty individuals had a deleterious RASA1 variant of which 29 were novel. Nine individuals had a variant of uncertain significance. Five large RASA1 deletions were detected, giving an overall deletion/duplication rate of 8.3% (5/60) among positive cases. Most (75.4%) individuals with a RASA1 variant had CMs, and 44.9% had an AVM/AVF. Clinical findings in several cases expand the RASA1 phenotype. Our data suggest that screening for large RASA1 deletions and duplications in this disorder is important and suggest that NGS multi-gene panel testing is beneficial for the molecular diagnosis of cases with complex vascular phenotypes.

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