Genetics of cerebral cavernous malformations.
The past few years have seen rapid advances in our understanding of the genetics and molecular biology of cerebral cavernous malformations (CCM). This article summarizes the recent cloning of the CCM1, CCM2, and CCM3 genes, which are responsible for autosomal dominant CCM, and also describes current hypotheses for their roles in integrin and p38 mitogen-activated protein kinase- mediated regulation of angiogenesis. A mouse model of CCM has been generated by mutation of the Ccm1 gene, and it indicates a role for that protein in arterial development. Future studies will probably focus on integration of data from each of the three CCM genes into a single model of the pathogenesis of cavernous malformation.
Plummer
Nicholas W
NW
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3175, Durham, NC 27710, USA.
Zawistowski
Jon S
JS
Marchuk
Douglas A
DA
D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D049109:Cell Proliferation; D002526:Cerebellar Diseases / Q000235:genetics*; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D000075927:KRIT1 Protein; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008958:Models, Molecular; D011518:Proto-Oncogene Proteins / Q000235:genetics
C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins