[Identification of a novel inheritable CCM1 gene mutation of 671del AT in a Chinese family with cerebral cavernous malformation].
OBJECTIVE
To investigate the hereditary characters of familial cerebral cavernous malformation (FCCM) and the novel gene mutation in a Chinese family.


METHODS
Head MRI examination and clinical neurological check were performed on a Chinese family with one proband of FCCM, female, 27 years old, and 16 family members, 9 males and 12 females, and 19 controls, including patients with sporadic CCM and other diseases and healthy persons. DNA was extracted from the white blood cells of the peripheral blood of the subjects. PCR and DNA direct sequencing were used to detect the mutation in CCM1 gene.


RESULTS
Head MRI found 11 FCCM patients in the 16 family members of the proband (69%), the youngest one being 4 years old, including multiple intracranial lesions in 7 patients and single lesion in 4. Relevant clinical manifestations were found in 6 out of the 11 family members. Nucleotide sequence analysis of the proband and other affected family members revealed a deletion frameshift mutation of A and T at nucleotides (nt) 671 and 672 in exon 13 of the CCM1 gene, resulting in truncated encoding KRIT1 protein. No mutation was detected in the healthy family members and the controls.


CONCLUSIONS
A novel inheritable CCM1 gene mutation of 671del AT has been found in patients with FCCM.
Mao
Ying
Y
Institute of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Zhao
Yao
Y
Zhou
Liang-fu
LF
Huang
Chuan-xin
CX
Shou
Xue-fei
XF
Gong
Jia-lei
JL
D000293:Adolescent; D000328:Adult; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins