A novel gene mutation (1292 deletion) in a Chinese family with cerebral cavernous malformations.

Objective: Hereditary cerebral cavernous malformations (CCMs) are characterized by focal abnormalities of small blood vessels in the brain and consequent hemorrhage and seizures. Previous studies of this type of CCM have mainly reported on this disorder in Hispanic and Caucasian cases. Here, we report on hereditary CCM in a Chinese family further characterized by a novel CCM1 gene mutation.

Methods: We investigated a family of 21 members, of whom 3 died and 16 of the survivors became the subjects of this study by brain magnetic resonance imaging.

Results: Brain magnetic resonance imaging demonstrated abnormal results in 11 members (69% penetrance), including multiple intracranial lesions in seven cases and single lesions in four cases. The clinical manifestation of CCM was found in these cases. The youngest patient was 4 years old. The remaining 5 members were normal. Nucleotide sequencing analysis of the family member representing the index case and other affected members revealed a deletion frameshift mutation of A and T at nucleotides 1292 and 1293 in exon 13 of the CCM1 gene, which resulted in truncated encoding Krev interaction trapped-1 protein.

Conclusion: Our results indicated a novel hereditary CCM1 gene mutation of 1292delAT, a finding that may contribute to the clarification of the mechanism of the disease.