Rath, Matthias and Spiegler, Stefanie and Nath, Neetika and Schwefel, Konrad and Di Donato, Nataliya and Gerber, Johannes and Korenke, G. Christoph and Hellenbroich, Yorck and Hehr, Ute and Gross, Stephanie and Sure, Ulrich and Zoll, Barbara and Gilberg, Eberhard and Kaderali, Lars and Felbor, Ute (2017) Constitutional de novo and postzygotic mutations in isolated cases of cerebral cavernous malformations. MOLECULAR GENETICS & GENOMIC MEDICINE, 5 (1). pp. 21-27. ISSN 2324-9269,
Full text not available from this repository. (Request a copy)Abstract
BackgroundCerebral cavernous malformations (CCM) are vascular lesions of the central nervous system that can be found in sporadic or autosomal dominantly inherited forms and manifest with headaches, seizures, and hemorrhagic stroke. The precise proportion of de novo mutations in the CCM1, CCM2, and CCM3 genes remains unknown. MethodsWe here present a series of six trios with de novo mutations that have been analyzed by amplicon deep sequencing to differentiate between constitutional and postzygotic mutations. ResultsIn one case, allelic ratios clearly indicated mosaicism for a CCM3 splice site mutation found in blood and buccal mucosa of a 2-year-old boy with multiple CCMs. The remaining five de novo mutations proved to be constitutional. In addition to three CCM3, two CCM1, and one CCM2 de novo point mutations, a deletion of the entire CCM3 gene was identified in an index case that most likely originated from an early postzygotic event. These are the first high-level mosaic mutations reported in blood samples of isolated CCM cases. ConclusionOur data demonstrate that de novo mutations in CCM1-3 might be more frequent than previously thought. Furthermore, amplicon deep sequencing is useful to discriminate between patients with constitutional and postzygotic mutations, and thereby improves genetic counseling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GERMLINE MUTATIONS; SOMATIC MUTATIONS; CCM1; GENES; CCM1; CCM2; CCM3; cerebral cavernous malformation; de novo mutation; deep sequencing; postzygotic mutation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:58 |
| Last Modified: | 12 Feb 2019 09:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/87 |
Actions (login required)
 |
View Item |
