New mutations of CCM1 gene in a family with familial multiple cerebral cavernous malformation
10.3760/cma.j.cn115354-20201010-00796
- VernacularTitle:一家族性多发CCM家系中 CCM1基因新发突变研究
- Author:
Feng ZHANG
1
;
Yiteng XUE
;
Xiaoming WEI
;
Li LIU
Author Information
1. 哈尔滨医科大学附属第一医院神经外科，哈尔滨 150001
- Keywords:
Cerebral cavernous malformation;
CCM1 gene;
Frame shift mutation
- From:
Chinese Journal of Neuromedicine
2021;20(7):689-694
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the characteristics of new mutations of CCM1 gene in a family with familial multiple cerebral cavernous malformation (CCM). Methods:A family with familial multiple CCM diagnosed in our hospital in 2013 and followed up for a long time were selected in our study. Peripheral blood samples and/or pathological tissue samples of some patients and healthy subjects in this family were collected for full exon sequencing of genomic DNA. Combined with the databases of Clin Var, HGMD and ExAC, the possible pathogenic genes in this family were screened by bioinformatics analysis; the three-dimensional structure prediction analysis of protein products was performed and Sanger sequencing was used to verify the pathogenic genes.Results:Whole exon sequencing showed that a novel deletion-frameshift mutation (c.1635delA) in CCM1 gene was noted in these patients, and this mutation leaded to deletion of reference nucleobase "T" ; this deletion had not been reported; while no above mutation was noted in the healthy subjects. Sanger sequencing showed that deletion of nucleobase "A" was noted in 1635 locus, No. 15 exon of CCM1 gene; this deletion would result in changes of CCM1 gene reading frame, which leaded to premature appearance of termination codon TAG at nucleotide of position 1652-1654. Three-dimensional structure prediction analysis showed that this new mutation might lead to the lack of Ferm-3 domain in the C-terminal of KRIT1 protein. Conclusion:The new deletion-frameshift mutation (c.1635delA) of CCM1 gene in this family leads to familial multiple CCM.
