1. Expanding the clinical and molecular findings in RASA1 capillary malformation-arteriovenous malformation
- Author
-
Jennifer L. R. Mayer, Pinar Bayrak-Toydemir, Jamie McDonald, Alejandro Berenstein, Angela E. Scheuerle, Peter Johnson, Marcie A. Steeves, Tracey Lewis, Francine Blei, Angela E. Lin, Michelle Sorscher, David A. Stevenson, J. Fredrik Grimmer, Gresham T. Richter, and Whitney Wooderchak-Donahue
- Subjects
0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Capillary malformation ,Adolescent ,Port-Wine Stain ,CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION ,Article ,Arteriovenous Malformations ,03 medical and health sciences ,symbols.namesake ,Young Adult ,0302 clinical medicine ,Gene duplication ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Child ,Genetics (clinical) ,Aged ,Sanger sequencing ,Comparative Genomic Hybridization ,business.industry ,Vascular malformation ,High-Throughput Nucleotide Sequencing ,Infant ,p120 GTPase Activating Protein ,Middle Aged ,medicine.disease ,Phenotype ,Parkes Weber syndrome ,Capillaries ,030104 developmental biology ,Child, Preschool ,Mutation ,symbols ,Female ,business ,030217 neurology & neurosurgery ,Comparative genomic hybridization - 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.
- Published
- 2018