High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: One-third of probands are minors

Molecular Genetics and Genomic Medicine

Volumn 2, Issue 2, 2014, Pages 176-185

  Spiegler, Stefanie ^a   Najm, Juliane ^a   Liu, Jian ^b   Gkalympoudis, Stephanie ^a   Schrëoder, Winnie ^a   Borck, Guntram ^c   Brockmann, Knut ^d   Elbracht, Miriam ^e   Fauth, Christine ^f   Ferbert, Andreas ^g   Freudenberg, Leonie ^h   Grasshoff, Ute ⁱ   Hellenbroich, Yorck ^j   Henn, Wolfram ^k   Hoffjan, Sabine ^l   Hëuning, Irina ^j   Korenke, G Christoph ^m   Kroisel, Peter M ⁿ   Kunstmann, Erdmute ^o   Mair, Martina ^k   Munk Schulenburg, Susanne ^p   Nikoubashman, Omid ^q   Pauli, Silke ^r   Rudnik Schëoneborn, Sabine ^e   Sudholt, Irene ^s   Sure, Ulrich ^t   Tinschert, Sigrid ^f,u   Wiednig, Michaela ⁿ   Zoll, Barbara ^r   Ginsberg, Mark H ^b   Felbor, Ute ^a   more..

^a UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c UNIVERSITY OF ULM   (Germany)

^d UNIVERSITY OF GÖTTINGEN   (Germany)

^e RWTH AACHEN UNIVERSITY   (Germany)

^f INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^g KLINIKUM KASSEL   (Germany)

^h UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

ⁱ UNIVERSITY OF TÜBINGEN   (Germany)

^j UNIVERSITY OF LÜBECK   (Germany)

^k SAARLAND UNIVERSITY   (Germany)

^l RUHR UNIVERSITY BOCHUM   (Germany)

^m Children's Hospital   (Germany)

ⁿ MEDICAL UNIVERSITY OF GRAZ   (Austria)

^o UNIVERSITY OF WÜRZBURG   (Germany)

^p UNIVERSITY OF FREIBURG   (Germany)

^q UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

^r University of Güottingen   (Germany)

^s UNIVERSITY OF ZURICH   (Switzerland)

^t UNIVERSITY HOSPITAL ESSEN   (Germany)

^u DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

more..

Author keywords

Age at disease onset; CCM1; CCM2; CCM3; Cerebral cavernous malformation; HEG1; Mutation detection rate; Predictive testing

Indexed keywords

EID: 84904661264     PISSN: None     EISSN: 23249269     Source Type: Journal    
DOI: 10.1002/mgg3.60     Document Type: Article

References (28)

1. Battistini, S., R. Rocchi, A. Cerase, A. Citterio, L. Tassi, G. Lando, et al. 2007. Clinical, magnetic resonance imaging, and genetic study of 5 Italian families with cerebral cavernous malformation. Arch. Neurol. 64:843–848.
2. Bergametti, F., C. Denier, P. Labauge, M. Arnoult, S. Boetto, M. Clanet, et al. 2005. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am. J. Hum. Genet. 76:42–51.
3. Cavée-Riant, F., C. Denier, P. Labauge, M. Céecillon, J. Maciazek, A. Joutel, et al. 2002. Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations. Eur. J. Hum. Genet. 10:733–740.
4. Davenport, W. J., A. M. Siegel, J. Dichgans, P. Drigo, I. Mammi, P. Pereda, et al. 2001. CCM1 gene mutations in families segregating cerebral cavernous malformations. Neurology 56:540–543.
5. Denier, C., S. Goutagny, P. Labauge, V. Krivosic, M. Arnoult, A. Cousin, et al. 2004. Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am. J. Hum. Genet. 74:326–337.
6. Denier, C., P. Labauge, F. Bergametti, F. Marchelli, F. Riant, M. Arnoult, et al. 2006. Genotype–phenotype correlations in cerebral cavernous malformations patients. Ann. Neurol. 60:550–556.
7. Gaetzner, S., S. Stahl, O. S€ur€uc߀u, A. Schaafhausen, B. Halliger-Keller, H. Bertalanffy, et al. 2007. CCM1 gene deletion identified by MLPA in cerebral cavernous malformation. Neurosurg. Rev. 30:155–159; discussion 159–160.
8. Gianfrancesco, F., M. Cannella, T. Martino, V. Maglione, T. Esposito, G. Innocenzi, et al. 2007. Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144:691–695.
9. Gingras, A. R., J. J. Liu, and M. H. Ginsberg. 2012. Structural basis of the junctional anchorage of the cerebral cavernous malformations complex. J. Cell Biol. 199:39–48.
10. Glading, A., J. Han, R. A. Stockton, and M. H. Ginsberg. 2007. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J. Cell Biol. 179:247–254.
11. Gunel, M., I. A. Awad, K. Finberg, J. A. Anson, G. K. Steinberg, H. H. Batjer, et al. 1996. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N. Engl. J. Med. 334:946–951.
12. Kleaveland, B., X. Zheng, J. J. Liu, Y. Blum, J. J. Tung, Z. Zou, et al. 2009. Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway. Nat. Med. 15:169–176.
13. Labauge, P., S. Laberge, L. Brunereau, C. Levy, and E. Tournier-Lasserve. 1998. Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Lancet 352:1892–1897.
14. Laberge-le Couteulx, S., H. H. Jung, P. Labauge, J. P. Houtteville, C. Lescoat, M. Céecillon, et al. 1999. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat. Genet. 23:189–193.
15. Limaye, N., L. M. Boon, and M. Vikkula. 2009. From germline towards somatic mutations in the pathophysiology of vascular anomalies. Hum. Mol. Genet. 18:R65–R74.
16. Liquori, C. L., M. J. Berg, A. M. Siegel, E. Huang, J. S. Zawistowski, T. Stoffer, et al. 2003. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am. J. Hum. Genet. 73:1459–1464.
17. Ng, B. H. K., E. Mulyadi, J. K. Pereira, S. Ghedia, J. Pinner, D. Mowat, et al. 2006. Familial cerebral cavernous haemangioma diagnosed in an infant with a rapidly growing cerebral lesion. Australas. Radiol. 50:583–590.
18. Nikoubashman, O., M. Wiesmann, E. Tournier-Lasserve, K. Mankad, M. Bourgeois, F. Brunelle, et al. 2013. Natural history of cerebral dot-like cavernomas. Clin. Radiol. 68: e453–e459.
19. Riant, F., F. Bergametti, H. Fournier, F. Chapon, S. Michalak-Provost, M. Céecillon, et al. 2013a. CCM3 mutations are associated with early-onset cerebral hemorrhage and multiple meningiomas. Mol. Syndromol. 4:165–172.
20. Riant, F., M. Céecillon, P. Saugier-Veber, and E. Tournier-Lasserve. 2013b. CCM molecular screening in a diagnosis context: novel unclassified variants leading to abnormal splicing and importance of large deletions. Neurogenetics 14:133–141.
21. Sahoo, T., E. W. Johnson, J. W. Thomas, P. M. Kuehl, T. L. Jones, C. G. Dokken, et al. 1999. Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum. Mol. Genet. 8:2325–2333.
22. Schreoder, W., J. Najm, S. Spiegler, M. Mair, J. Viera, W. Henn, et al. 2014. Predictive genetic testing of at-risk relatives requires analysis of all CCM genes after identification of an unclassified CCM1 variant in an individual affected with cerebral cavernous malformations. Neurosurg. Rev. 37:161–165.
23. Siegel, A. M., H. Bertalanffy, J. J. Dichgans, C. E. Elger, H. Hopf, N. Hopf, et al. 2005. Familiäre Kavernome des Zentralnervensystems. Eine klinische und genetische Studie an 15 deutsche Familien. (Familial cavernous malformations of the central nervous system. A clinical and genetic study of 15 German families). Nervenarzt 76:175–180.
24. Stahl, S., S. Gaetzner, K. Voss, B. Brackertz, E. Schleider, O. S€ur€uc߀u, et al. 2008. Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex. Hum. Mutat. 29:709–717.
25. Süurüucßüu, O., U. Sure, S. Gaetzner, S. Stahl, L. Benes, H. Bertalanffy, et al. 2006. Clinical impact of CCM mutation detection in familial cavernous angioma. Childs Nerv. Syst. 22:1461–1464.
26. Verlaan, D. J., W. J. Davenport, H. Stefan, U. Sure, A. M. Siegel, and G. A. Rouleau. 2002. Cerebral cavernous malformations: mutations in Krit1. Neurology 58:853–857.
27. Voss, K., S. Stahl, B. M. Hogan, J. Reinders, E. Schleider, S. Schulte-Merker, et al. 2009. Functional analyses of human and zebrafish 18-amino acid in-frame deletion pave the way for domain mapping of the cerebral cavernous malformation 3 protein. Hum. Mutat. 30:1003–1011.
28. Zhang, J., R. E. Clatterbuck, D. Rigamonti, and H. C. Dietz. 2000. Mutations in KRIT1 in familial cerebral cavernous malformations. Neurosurgery 46:1272–1277; discussion 1277–1299.