title: Features of a Chinese family with cerebral cavernous malformation induced by a novel CCM1 gene mutation.
abstract: BACKGROUND
  Familial cerebral cavernous malformations (CCMs), characterized by hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular anomalies of the central nervous system. Familial CCMs is an autosomal dominant inherited disorder and three CCM genes have been identified. We report a Chinese family with CCMs and intend to explore clinical, pathological, magnetic resonance imaging (MRI) features and pathogenic gene mutation of this family.
  
  
  METHODS
  Totally 25 family members underwent brain MRI examination and clinical check. Two patients with surgical indications had surgical treatment and the specimens were subjected to histopathological and microstructural examination. In addition, polymerase chain reaction (PCR) and direct sequencing were performed with genomic DNA extracted from 25 family members' blood samples for mutation detection.
  
  
  RESULTS
  Brain MRI identified abnormal results in seven family members. All of them had multiple intracranial lesions and four cases had skin cavernous hemangioma. T2-weighted sequence showed that the lesions were typically characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence was more sensitive to find micro-cavernous hemangiomas. There was a wide range in the clinical manifestations as well as the age of onset in the family. The youngest patient was an 8-year-old boy with least intracranial lesions. Histopathological and microstructural examination showed that CCMs were typically discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages of illness evolution. They were formed by abnormally enlarged sinusoids and the thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was identified by mutation detection in the seven patients. But unaffected members and healthy controls did not carry this mutation.
  
  
  CONCLUSIONS
  The clinical manifestations were heterogenic within this family. We identified a novel mutation (c.1396delT) was the disease-causing mutation for this family and extended the mutational spectrum of CCMs.
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Xue-Wu
authors.initials: XW
authors.lastname: Liu
authors.forename: Nora
authors.initials: N
authors.lastname: Lee
authors.forename: Qi-Ji
authors.initials: QJ
authors.lastname: Liu
authors.forename: Wen-Na
authors.initials: WN
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Kun-Kun
authors.initials: KK
authors.lastname: Wei
authors.forename: Shan
authors.initials: S
authors.lastname: Qiao
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Chi
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins