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Loss of heterozygosity in CCM2 cDNA revealing a structural variant causing multiple cerebral cavernous malformations.
Chaussenot, Annabelle; Ayrignac, Xavier; Chatron, Nicolas; Granchon-Riolzir, Terry; Labauge, Pierre; Tournier-Lasserve, Elisabeth; Riant, Florence.
  • Chaussenot A; Department of Medical Genetics, Hôpital de l'Archet 2, CHU de Nice, Nice, France.
  • Ayrignac X; Department of Neurology, Gui de Chauliac Montpellier University Hospital, Montpellier University, Montpellier, France.
  • Chatron N; Department of Medical Genetics, Hospices Civils de Lyon, Groupe Hospitalier Est, Bron, France.
  • Granchon-Riolzir T; Laboratoire AURAGEN (Plan France Médecine Génomique 2025), Lyon, France.
  • Labauge P; Department of Neurovascular Molecular Genetics AP-HP, Saint-Louis Hospital, Paris, France.
  • Tournier-Lasserve E; Reference Center for Rare Vascular Diseases of the Central Nervous System and the Retina (CERVCO), APHP Lariboisiere Hospital, Paris, France.
  • Riant F; Department of Neurology, Gui de Chauliac Montpellier University Hospital, Montpellier University, Montpellier, France.
Eur J Hum Genet ; 32(7): 876-878, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38755314
ABSTRACT
Loss-of-function variants in CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10 genes 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 CCM2 was 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 CCM2 gene, preventing normal mRNA synthesis. These data underline the importance of WGS in undiagnosed patients with typical multiple CCM.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linaje / Pérdida de Heterocigocidad / Hemangioma Cavernoso del Sistema Nervioso Central Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linaje / Pérdida de Heterocigocidad / Hemangioma Cavernoso del Sistema Nervioso Central Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2024 Tipo del documento: Article