Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation

Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) responsible for CCM. Here, we characterized a four-generation family diagnosed with CCM and identified a novel heterozygous mutation c.1159C>T, p.Q387X in KRIT1 gene by whole exome sequencing and Sanger sequencing. The Q387X mutation resulted in premature termination of KRIT1 protein, which was predicted to be deleterious by the ACMG/AMP 2015 guideline. Our results provide novel genetic evidence support that KRIT1 mutations cause CCM, and are helpful to the treatment and genetic diagnosis of CCM.

Automated summary

In this study, a novel heterozygous mutation (c.1159C>T, p.Q387X) in the KRIT1 gene was identified in a four-generation family with cerebral cavernous malformation (CCM). This mutation resulted in premature termination of the KRIT1 protein, providing further evidence that KRIT1 mutations are a cause of CCM. These findings are important for the treatment and genetic diagnosis of CCM.