Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations.
OBJECTIVE
Pathogenesis of cerebral venous malformation (CVM) is unknown. Because of coexistence of CVM and cerebral cavernous malformations (CCM), some studies have suggested that these 2 entities share a common origin and pathogenetic mechanism.


METHODS
We have identified and ascertained over 200 families with CCM. Among these, 1 unique family was found to have members affected by both disorders. We have performed mutational analysis in all 3 CCM genes, KRIT1, Malcavernin, and PDCD10, to identify the causative gene in the family.


RESULTS
Mutational analysis revealed a frameshift mutation affecting exon 19 of the CCM1 gene (KRIT1) in members with CCM, whereas no such mutation was observed in the member with CVM.


CONCLUSIONS
These findings support the hypothesis that CVM and CCM are 2 distinct entities with different pathogenetic mechanisms. This data further supports the hypothesis that CVM has a distinct biology and clinical behavior when compared to CCM. CVM is a benign developmental anomaly and should be managed separately from CCM.
Guclu
Bulent
B
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.
Ozturk
Ali K
AK
Pricola
Katie L
KL
Seker
Askin
A
Ozek
Memet
M
Gunel
Murat
M
D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001808:Blood Vessels / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D005786:Gene Expression Regulation; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000175:diagnosis* / Q000235:genetics*; D000075927:KRIT1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins