In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 5, No. 1 ( 2017-01), p. 21-27
Kurzfassung:
Cerebral 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 CCM 1 , CCM 2 , and CCM 3 genes remains unknown. Methods We 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. Results In one case, allelic ratios clearly indicated mosaicism for a CCM 3 splice site mutation found in blood and buccal mucosa of a 2‐year‐old boy with multiple CCM s. The remaining five de novo mutations proved to be constitutional. In addition to three CCM 3 , two CCM 1 , and one CCM 2 de novo point mutations, a deletion of the entire CCM 3 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. Conclusion Our data demonstrate that de novo mutations in CCM 1‐3 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.
Materialart:
Online-Ressource
ISSN:
2324-9269
,
2324-9269
DOI:
10.1002/mgg3.2017.5.issue-1
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2017
ZDB Id:
2734884-2