A Novel CCM2 Gene Mutation Associated With Cerebral Cavernous Malformation

Overview

Journal Front Neurol

Specialty Neurology

Date 2020 Mar 3

PMID 32117029

Citations 7

Authors

Lipeng Yang

Jian Wu

Jing Zhang

Affiliations

Soon will be listed here.

Abstract

Cerebral cavernous malformations (CCMs) are the second most prevalent type of vascular malformation within the central nervous system. CCMs occur in two forms-sporadic and familial-the latter of which has an autosomal dominant mode of inheritance with incomplete penetrance and variable clinical expressivity. There are three genes considered to be associated with CCMs,-, which codes for KRIT1 protein; , which codes for MGC4607 protein; and , which codes for PDCD10 protein. To date, more than 74 gene mutations of CCM2 have been reported, and ~45% are deletion mutations. In this article, we disclose a novel genetic variant (c.755delC, p.S252fs40X) identified in a Chinese family to enrich the database of CCM2 genotypes.

Citing Articles

Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing.

Smith J, Rai V Biomedicines. 2024; 12(9).

PMID: 39335453 PMC: 11429312. DOI: 10.3390/biomedicines12091939.

Peripheral macrophages in the development and progression of structural cerebrovascular pathologies.

Lauzier D, Srienc A, Vellimana A, Dacey Jr R, Zipfel G J Cereb Blood Flow Metab. 2023; 44(2):169-191.

PMID: 38000039 PMC: 10993883. DOI: 10.1177/0271678X231217001.

Molecular genetic features and clinical manifestations in Chinese familial cerebral cavernous malformation: from a novel KRIT1/CCM1 mutation (c.1119dupT) to an overall view.

Chen Y, Dong X, Wang Y, Lv H, Chen N, Wang Z Front Neurosci. 2023; 17:1184333.

PMID: 37214396 PMC: 10192864. DOI: 10.3389/fnins.2023.1184333.

A novel KRIT1/CCM1 mutation accompanied by a NOTCH3 mutation in a Chinese family with multiple cerebral cavernous malformations.

Li C, Liu P, Huang W, Wang H, Ma K, Zhuo L Neurogenetics. 2023; 24(2):137-146.

PMID: 36892712 DOI: 10.1007/s10048-023-00714-y.

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms.

Butnariu L, Gorduza E, Florea L, Tarca E, Moisa S, Trandafir L Int J Mol Sci. 2022; 23(20).

PMID: 36293054 PMC: 9603778. DOI: 10.3390/ijms232012199.

References

Fisher O, Liu W, Zhang R, Stiegler A, Ghedia S, Weber J . Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. J Biol Chem. 2014; 290(5):2842-53. PMC: 4317034. DOI: 10.1074/jbc.M114.616433. View

Jiang X, Padarti A, Qu Y, Sheng S, Abou-Fadel J, Badr A . Alternatively spliced isoforms reveal a novel type of PTB domain in CCM2 protein. Sci Rep. 2019; 9(1):15808. PMC: 6825194. DOI: 10.1038/s41598-019-52386-0. View

Cavalcanti D, Kalani M, Martirosyan N, Eales J, Spetzler R, Preul M . Cerebral cavernous malformations: from genes to proteins to disease. J Neurosurg. 2011; 116(1):122-32. DOI: 10.3171/2011.8.JNS101241. View

Rinaldi C, Bramanti P, Scimone C, Donato L, Alafaci C, DAngelo R . Relevance of CCM gene polymorphisms for clinical management of sporadic cerebral cavernous malformations. J Neurol Sci. 2017; 380:31-37. DOI: 10.1016/j.jns.2017.06.043. View

Chang C, Hsu P, Wei K, Chang C, Fung H, Hsih M . CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan. Sci Rep. 2019; 9(1):12387. PMC: 6712018. DOI: 10.1038/s41598-019-48448-y. View

Wang K, Wu D, Zhang B, Zhao G . Novel and Gene Variants in Chinese Families With Cerebral Cavernous Malformations. Front Neurol. 2019; 9:1128. PMC: 6308150. DOI: 10.3389/fneur.2018.01128. View

Nardella G, Visci G, Guarnieri V, Castellana S, Biagini T, Bisceglia L . A single-center study on 140 patients with cerebral cavernous malformations: 28 new pathogenic variants and functional characterization of a PDCD10 large deletion. Hum Mutat. 2018; 39(12):1885-1900. DOI: 10.1002/humu.23629. View

Pan L, Yan J, Wu L, Zhang M . Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23. Proc Natl Acad Sci U S A. 2009; 106(14):5575-80. PMC: 2667052. DOI: 10.1073/pnas.0901819106. View

Li X, Fisher O, Boggon T . The cerebral cavernous malformations proteins. Oncotarget. 2015; 6(32):32279-80. PMC: 4741677. DOI: 10.18632/oncotarget.5443. View

10.

Kim J . Introduction to cerebral cavernous malformation: a brief review. BMB Rep. 2016; 49(5):255-62. PMC: 5070704. DOI: 10.5483/bmbrep.2016.49.5.036. View

11.

Jih K, Chung C, Chang Y, Hung P, Soong B, Liao Y . Mutational analysis of CCM1, CCM2 and CCM3 in a Han Chinese cohort with multiple cerebral cavernous malformations in Taiwan. Clin Genet. 2018; 94(3-4):389-390. DOI: 10.1111/cge.13377. View

12.

Scimone C, Donato L, Katsarou Z, Bostantjopoulou S, DAngelo R, Sidoti A . Two Novel and Mutations in Patients Affected by Cerebral Cavernous Malformations: New Information on Penetrance. Front Neurol. 2018; 9:953. PMC: 6246743. DOI: 10.3389/fneur.2018.00953. View

13.

Fisher O, Deng H, Liu D, Zhang Y, Wei R, Deng Y . Structure and vascular function of MEKK3-cerebral cavernous malformations 2 complex. Nat Commun. 2015; 6:7937. PMC: 4526114. DOI: 10.1038/ncomms8937. View

14.

Zawistowski J, Stalheim L, Uhlik M, Abell A, Ancrile B, Johnson G . CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum Mol Genet. 2005; 14(17):2521-31. DOI: 10.1093/hmg/ddi256. View

15.

Zabramski J, Wascher T, Spetzler R, Johnson B, Golfinos J, Drayer B . The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg. 1994; 80(3):422-32. DOI: 10.3171/jns.1994.80.3.0422. View

16.

Gunel M, Awad I, Anson J, Lifton R . Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. Proc Natl Acad Sci U S A. 1995; 92(14):6620-4. PMC: 41570. DOI: 10.1073/pnas.92.14.6620. View

17.

Riant F, Cecillon M, Saugier-Veber P, Tournier-Lasserve E . CCM molecular screening in a diagnosis context: novel unclassified variants leading to abnormal splicing and importance of large deletions. Neurogenetics. 2013; 14(2):133-41. DOI: 10.1007/s10048-013-0362-0. View

18.

DAngelo R, Alafaci C, Scimone C, Ruggeri A, Salpietro F, Bramanti P . Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients. Biomed Res Int. 2013; 2013:459253. PMC: 3766605. DOI: 10.1155/2013/459253. View

19.

Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M . Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol. 2006; 60(5):550-556. DOI: 10.1002/ana.20947. View

20.

Fisher O, Zhang R, Li X, Murphy J, Demeler B, Boggon T . Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus. FEBS Lett. 2012; 587(3):272-7. PMC: 3558538. DOI: 10.1016/j.febslet.2012.12.011. View