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| Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations |
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| Author(s): Eerola I, Boon LM, Mulliken JB, Burrows PE, Dompmartin A, Watanabe S, Vanwijck R, Vikkula M |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 73 Issue: 6 Pages: 1240-1249 Published: DEC 2003 |
| Times Cited: 57 References: 49 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Vikkula, M (reprint author), Univ Catholique Louvain, Christian du Duve Inst Cellular Pathol, Lab Human Mol Genet, Ave Hippocrate 74 5,BP 75-39, B-1200 Brussels, Belgium |
Addresses:
1. Univ Catholique Louvain, Christian du Duve Inst Cellular Pathol, Lab Human Mol Genet, B-1200 Brussels, Belgium
2. Univ Catholique Louvain, Clin Univ St Luc, Div Plast Surg, Ctr Vasc Anomalies, B-1200 Brussels, Belgium
3. Harvard Univ, Sch Med, Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02114 USA
4. Harvard Univ, Sch Med, Childrens Hosp, Div Plast Surg, Boston, MA 02114 USA
5. Harvard Univ, Sch Med, Childrens Hosp, Div Intervent Radiol, Boston, MA 02114 USA
6. CHU Caen, Div Dermatol, Caen, France
7. Showa Univ, Sch Med, Dept Plast & Reconstruct Surg, Tokyo 142, Japan |
| Publisher: UNIV CHICAGO PRESS, 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 756PW |
| ISSN: 0002-9297 |
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