We analyzed CCM1/KRIT1, CCM2/MGC4607, and CCM3/PCDP10 among 41 patients with cerebral cavernous malformation. Then, we found two novel pathological variants of CCM1 (c.1846delA and c.485+1G>C) and one novel variants of CCM2 (c.401_402insGCCC).. CCM1 and CCM2 mutations in patients with cerebral cavernous malformation in an ethnic Chinese population in Taiwan

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by clustered enlarged capillary-like channels in the central nervous system. The related genes include CCM1/Krev interaction trapped-1, CCM2/MGC4607, and CCM3/programmed cell death protein 10. We aimed to identify genetic mutations in an ethnic Chinese population in Taiwan. We recruited 95 patients with multiple CCMs or a single lesion with a relevant family history. Sanger sequencing were performed for 41 patients. Mutation sites were found with sequence alignment tools, and clinical significance of mutations was predicted by mutation predictors and classified by American College of Medical Genetics and Genomics standards and guideline. Several mutations were found in seven patients, including four unrelated patients and three affected members of one family. Two novel mutations causing early truncation comprised a deletion mutation in the exon 18 of CCM1 (c.1846delA; p.Glu617LysfsTer44) and an insertion mutation in the exon 4 of CCM2 (c.401_402insGCCC, p.Ile136AlafsTer4). One novel point mutation with pathological significance was c.485+1G>C as a splice site mutation at the beginning of intron 8 of CCM1. In this study, we identified novel mutation sites related to CCM in an ethnic Chinese population in Taiwan.