Large germline deletions and duplication in isolated cerebral cavernous malformation patients
- 88 Downloads
Cerebral cavernous malformations (CCM) are vascular lesions that predispose to headaches, seizures, and hemorrhagic stroke. Hereditary CCMs are usually associated with the occurrence of multiple CCMs and occur with a frequency of 1:2,000 to 1:10,000. In this study, eight isolated cases with multiple CCMs but no CCM1-3 point mutation were analyzed using the multiplex ligation-dependent probe amplification assay. Four genomic rearrangements were identified including a previously unreported large duplication within the CCM1 gene and a novel deletion involving the entire coding region of the CCM2 gene. Consequently, systematic screening for CCM deletions/duplications is recommended.
KeywordsVascular malformations Cerebral cavernous malformation MLPA Deletion Duplication
The authors thank the patients for their cooperation. Ute Felbor receives an Emmy Noether grant from the Deutsche Forschungsgemeinschaft (Fe 432/6–5) and is supported by a grant from the Bavarian Genome Network. The experiments comply with the current German laws.
Disclosure The authors have reported no conflicts of interest.
- 3.Denier C, Goutagny S, Labauge P, Krivosic V, Arnoult M, Cousin A, Benabid AL, Comoy J, Frerebeau P, Gilbert B, Houtteville JP, Jan M, Lapierre F, Loiseau H, Menei P, Mercier P, Moreau JJ, Nivelon-Chevallier A, Parker F, Redondo AM, Scarabin JM, Tremoulet M, Zerah M, Maciazek J, Tournier-Lasserve E (2004) Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet 74:326–337PubMedCrossRefGoogle Scholar
- 4.Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, Coubes P, Echenne B, Ibrahim R, Irthum B, Jacuet G, Lonjon M, Moreau JJ, Neau JP, Parker F, Tremoulet M, Tournier-Lasserve E (2005) Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet 76:42–51PubMedCrossRefGoogle Scholar
- 5.Gaetzner S, Stahl S, Sürücü O, Schaafhausen A, Halliger-Keller B, Bertalanffy H, Sure U, Felbor U (2006) CCM1 gene deletion identified by MLPA in cerebral cavernous malformation. Neurosurg Rev (in press) doi:10.1007/s10143-006-0057-1