First large genomic inversion in familial cerebral cavernous malformation identified by whole genome sequencing

Neurogenetics - Tập 19 - Trang 55-59 - 2017
Stefanie Spiegler1, Matthias Rath1, Sabine Hoffjan2, Philipp Dammann3, Ulrich Sure3, Axel Pagenstecher4, Tim Strom5,6, Ute Felbor1
1Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
2Department of Human Genetics, Ruhr-University, Bochum, Germany
3Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
4Department of Neuropathology, University Hospital Giessen and Marburg, Marburg, Germany
5Institute of Human Genetics, Technische Universität München, Munich, Germany
6Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

Tóm tắt

Familial cerebral cavernous malformations (CCMs) predispose to seizures and hemorrhagic stroke. Molecular genetic analyses of CCM1, CCM2, and CCM3 result in a mutation detection rate of up to 98%. However, only whole genome sequencing (WGS) in combination with the Manta algorithm for analyses of structural variants revealed a heterozygous 24 kB inversion including exon 1 of CCM2 in a 12-year-old boy with familial CCMs. Its breakpoints were fine-mapped, and quantitative analysis on RNA confirmed reduced CCM2 expression. Our data expand the spectrum of CCM mutations and indicate that the existence of a fourth CCM disease gene is rather unlikely.

Tài liệu tham khảo

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