1. Constitutional mosaicism in RASA1-related capillary malformation-arteriovenous malformation
- Author
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Noelia Agra, Victor Martinez-Glez, Juan Carlos López-Gutiérrez, Gema Gordo, Pablo Lapunzina, Marta Feito, Pilar Mendez, and Lara Rodriguez-Laguna
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Genotype ,Computed Tomography Angiography ,media_common.quotation_subject ,Nonsense ,Port-Wine Stain ,Tissue sample ,CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION ,030105 genetics & heredity ,Biology ,Germline ,Recurrence risk ,Arteriovenous Malformations ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetics (clinical) ,Alleles ,Genetic Association Studies ,media_common ,Mosaicism ,p120 GTPase Activating Protein ,Phenotype ,Capillaries ,030104 developmental biology ,Amino Acid Substitution ,Mutation ,Female - Abstract
Capillary malformation-arteriovenous malformation (CM-AVM) is caused by germline RASA1 and EPHB4 alterations. RASA1 intralesional second hits have also been reported. Here we report RASA1 constitutional mosaicism, defined here as the presence of a mosaic variant in all cell types of an individual, in two patients with CM-AVM. High-throughput sequencing was used to search for RASA1 pathogenic variants in blood samples from two unrelated patients with CM-AVM. An affected tissue sample from one of the patients was also analyzed. Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. Constitutional mosaicism has implications for accurate molecular diagnosis and recurrence risk and helps to explain the great phenotypic variability in CM-AVM.
- Published
- 2018