tailieunhanh - Báo cáo khoa học: Recent insights into cerebral cavernous malformations: the molecular genetics of CCM

Cerebral cavernous malformations (CCM) are vascular lesions which can occur as a sporadic (80% of the cases) or familial autosomal dominant form (20%). Three CCM genes have been identified: CCM1⁄KRIT1, CCM2⁄MGC4607and CCM3⁄PDCD10. Almost 80% of CCM patients affected with a genetic form of the disease harbor a heterozygous germline mutation in one of these three genes. | MINIREVIEW Recent insights into cerebral cavernous malformations the molecular genetics of CCM Florence Riant1 2 Francoise Bergametti2 Xavier Ayrignac2 Gwenola Boulday2 and Elisabeth Tournier-Lasserve1 2 1 AP-HP HopitalLariboisiere Laboratoire de Genetique Paris France 2 INSERM UMR-S 740 Universite Paris 7 Diderot France Keywords angiogenesis CCM1 CCM2 CCM3 cerebralcavernous malformations cerebral hemorrhage KRIT1 PDCD10 stroke vascular malformations Correspondence E. Tournier-Lasserve INSERM UMR-S 740 Universite Paris7 Diderot 10 Avenue du Verdun 75010 Paris France Fax 33 157278594 Tel 33 157278593 E-mail tournier-lasserve@ Received 1 August 2009 revised 4 November 2009 accepted 4 December 2009 doi Cerebral cavernous malformations CCM are vascular lesions which can occur as a sporadic 80 of the cases or familial autosomal dominant form 20 . Three CCM genes have been identified CCM1 KRIT1 CCM2 MGC4607 and CCM3 PDCD10. Almost 80 of CCM patients affected with a genetic form of the disease harbor a heterozygous germline mutation in one of these three genes. Recent work has shown that a two-hit mechanism is involved in CCM pathogenesis which is caused by a complete loss of any of the three CCM proteins within endothelial cells lining the cavernous capillary cavities. These data were an important step towards the elucidation of the mechanisms of this condition. Introduction Cerebral cavernous malformations CCM OMIM 116860 are vascular lesions histologically characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. From large series based on necropsy and or magnetic resonance imaging MRI studies their prevalence in the general population has been estimated to be close to . Most CCMs are located within the central nervous system but they sometimes affect either the retina or the skin 1 . CCM occur both sporadically and in a familial context. The proportion of familial cases .