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Constitutional mosaicism in RASA1-related capillary malformation-arteriovenous malformation.

Gema GordoLara Rodriguez-LagunaNoelia AgraPilar MendezMarta FeitoPablo LapunzinaJuan C Lopez-GutierrezVictor Martínez-González
Published in: Clinical genetics (2019)
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.
Keyphrases
  • end stage renal disease
  • newly diagnosed
  • ejection fraction
  • prognostic factors
  • stem cells
  • bone marrow
  • dna methylation
  • mesenchymal stem cells
  • dna repair