Taking advantage of an Italian research network with a coordination center at the University of Torino, we previously performed the molecular genetic analyses of the three known CCM genes in a large Italian cohort of CCM patients and at-risk relatives using the traditional Sanger exon sequencing approach, showing that 67% the familial cases had a mutation in KRIT1, 5.5% in CCM2 and 5.5% in CCM3, whereas no mutations in CCM genes were detected in the remaining 22% of cases [45]. Here, CCM2 is linked to cerebral cavernous malformation.