A novel CCM3 mutation associated with cerebral cavernous malformation in a Chinese family.

Background: Cerebral cavernous malformation (CCM), especially the familial form, is a relatively rare congenital and occult vascular disease of the central nervous system. The familial form of CCM has been linked to three different genes: //, and /; however, the genetic basis of CCM is not well understood. The / is the most recent gene to be identified that results in worse clinical symptoms. Early diagnosis and treatment is important for patient prognosis.

Case Report: The proband is a 38-year-old male who has been suffering from weakness in the limbs for 7 months. Investigation of his family history revealed that his mother also suffered from limbs paralysis and had been bedridden for a long time. His older brother suffered from headache for years, whereas his younger brother was asymptomatic. Brain computed tomography analysis of all family members showed multiple high-density shadows. Subsequently, magnetic resonance imaging analysis identified more prominent and similar multiple intracranial lesions in all family members. The lesions were hypo-intense, or showed mixed signs on T1-weighted imaging, and were significantly more intense on T2-weighted imaging. To understand the genetic basis of the disease in the family, DNA sequencing analysis was performed. A novel deletion mutation in the / gene was identified in the proband and his relatives. The deletion resulted in a frameshift mutation and premature termination of translation of the protein, and potentially caused the disease in this family.

Conclusions: Our study identified a novel / heterozygous deletion (c.165delT) associated with CCM. This finding expands the gene mutation profile, which will be beneficial for genetic counseling and clinical therapy.