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Loss of heterozygosity in CCM2cDNA revealing a structural variant causing multiple cerebral cavernous malformations
- Source :
- European Journal of Human Genetics: EJHG; 20240101, Issue: Preprints p1-3, 3p
- Publication Year :
- 2024
-
Abstract
- Loss-of-function variants in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations. However, genomic DNA sequencing combined with large rearrangement screening fails to detect a pathogenic variant in 5% of the patients. We report a family with two affected members harboring multiple CCM lesions, one with severe hemorrhages and one asymptomatic. No causative variant was detected using DNA sequencing of the three CCM genes, CNV detection analysis, and RNA sequencing. However, a loss of heterozygosity in CCM2was observed on cDNA sequences in one of the two affected members, which strongly suggested that this locus might be involved. Whole genome sequencing (WGS) identified a balanced structural variant on chromosome 7 with a breakpoint interrupting the CCM2gene, preventing normal mRNA synthesis. These data underline the importance of WGS in undiagnosed patients with typical multiple CCM.
Details
- Language :
- English
- ISSN :
- 10184813 and 14765438
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- European Journal of Human Genetics: EJHG
- Publication Type :
- Periodical
- Accession number :
- ejs66399900
- Full Text :
- https://doi.org/10.1038/s41431-024-01626-7