Erschienen in:
02.12.2017 | Short Communication
First large genomic inversion in familial cerebral cavernous malformation identified by whole genome sequencing
verfasst von:
Stefanie Spiegler, Matthias Rath, Sabine Hoffjan, Philipp Dammann, Ulrich Sure, Axel Pagenstecher, Tim Strom, Ute Felbor
Erschienen in:
Neurogenetics
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Ausgabe 1/2018
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Abstract
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.