[PDF][PDF] Capillary malformation–arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations

I Eerola, LM Boon, JB Mulliken, PE Burrows… - The American Journal of …, 2003 - cell.com
I Eerola, LM Boon, JB Mulliken, PE Burrows, A Dompmartin, S Watanabe, R Vanwijck…
The American Journal of Human Genetics, 2003cell.com
Capillary malformation (CM), or" port-wine stain," is a common cutaneous vascular anomaly
that initially appears as a red macular stain that darkens over years. CM also occurs in
several combined vascular anomalies that exhibit hypertrophy, such as Sturge-Weber
syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome. Occasional familial
segregation of CM suggests that there is genetic susceptibility, underscored by the
identification of a large locus, CMC1, on chromosome 5q. We used genetic fine mapping …
Capillary malformation (CM), or "port-wine stain," is a common cutaneous vascular anomaly that initially appears as a red macular stain that darkens over years. CM also occurs in several combined vascular anomalies that exhibit hypertrophy, such as Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Parkes Weber syndrome. Occasional familial segregation of CM suggests that there is genetic susceptibility, underscored by the identification of a large locus, CMC1, on chromosome 5q. We used genetic fine mapping with polymorphic markers to reduce the size of the CMC1 locus. A positional candidate gene, RASA1, encoding p120-RasGAP, was screened for mutations in 17 families. Heterozygous inactivating RASA1 mutations were detected in six families manifesting atypical CMs that were multiple, small, round to oval in shape, and pinkish red in color. In addition to CM, either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome was documented in all the families with a mutation. We named this newly identified association caused by RASA1 mutations "CM-AVM," for capillary malformation–arteriovenous malformation. The phenotypic variability can be explained by the involvement of p120-RasGAP in signaling for various growth factor receptors that control proliferation, migration, and survival of several cell types, including vascular endothelial cells.
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