Germline mutations in the CCM1 gene, encoding krit1, cause cerebral cavernous malformations

Mutations in the Krit1 gene have been recently discovered as the cause of hereditary cerebral cavernous angioma We sought the possibility that de novo, noninherited mutations of Krit1 also cause cavernous angioma A patient with two cerebral malformations carries a heterozygous deletion of two base pairs (741delTC) in exon VI of the Krit1 gene. The deletion initiates a frameshift mutation that, 23 amino acids downstream, encodes a TAA stop triplet replacing a CAT triplet of histidine at exon VII (H271X). Magnetic resonance images of the parents were normal, neither parent carries the 741delTC mutation, and both bear the wild-type sequence of exon VI. These findings document a de novo germline mutation in Krit1 gene that causes cerebral cavernous malformations.