Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Hum Mol Genet. 2009 Mar 1;18(5):911-8. doi: 10.1093/hmg/ddn420. Epub 2008 Dec 16.

A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.

Author information

  • 1Department of Neuropathology, University of Marburg, Germany.

Abstract

Cavernous vascular malformations occur with a frequency of 1:200 and can cause recurrent headaches, seizures and hemorrhagic stroke if located in the brain. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein expression depending on the inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein but not for the two others. In addition to proving loss of function at the protein level, our data are the first to demonstrate endothelial cell mosaicism within cavernous tissues and provide clear pathogenetic evidence that the endothelial cell is the cell of disease origin.

PMID:
19088124
[PubMed - indexed for MEDLINE]
PMCID:
PMC2640205
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1.
Figure 2.
Figure 3.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk