Description of Two Families with New Mutations in Familial Cerebral Cavernous Malformations Genes

Pablo Iruzubieta; David Campo-Caballero; Jon Equiza; Inés Albajar; Naroa Sulibarría; Raquel Sáez; Naiara Andrés; Elisabet Mondragón; Miren Zulaica; Ana de Arce; Miguel Urtasun; Adolfo López de Munain

doi:10.1016/j.jstrokecerebrovasdis.2021.106130

Description of Two Families with New Mutations in Familial Cerebral Cavernous Malformations Genes

J Stroke Cerebrovasc Dis. 2021 Dec;30(12):106130. doi: 10.1016/j.jstrokecerebrovasdis.2021.106130. Epub 2021 Sep 29.

Authors

Affiliations

¹ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain; Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain. Electronic address: [email protected].
² Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
³ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
⁴ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
⁵ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
⁶ Genetics Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
⁷ Neurology Department, Hospital of Mendaro, Osakidetza, Mendaro, Spain. Electronic address: [email protected].
⁸ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
⁹ Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain. Electronic address: [email protected].
¹⁰ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
¹¹ Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain. Electronic address: [email protected].
¹² Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain; Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain; Neurosciences Department, Basque Country University, San Sebastián, Spain; Centro de Investigación en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto Carlos III, Madrid, Spain. Electronic address: [email protected].

PMID: 34597987
DOI: 10.1016/j.jstrokecerebrovasdis.2021.106130

Abstract

Cerebral cavernous malformations (CCMs) are dilated aberrant leaky capillaries located in the Central Nervous System. Familial CCM is an autosomal dominant inherited disorder related to mutations in KRIT1, Malcavernin or PDCD10. We show two unrelated families presenting familial CCM due to two new mutations in KRIT1 and PDCD10, producing truncated proteins. Clinical phenotype was highly variable among patients from asymptomatic individuals to diplopia, seizures or severe intracranial hemorrhage. PDCD10 patients usually show a more aggressive course and they frequently showed multiple meningiomas. This work provides evidence for the pathogenicity of two new mutations in CCM genes and supports previous findings regarding familial CCM and multiple meningiomas.

Keywords: Cavernoma; Cerebral cavernous malformation; Intracranial hemorrhage; KRIT1; Meningioma; PDCD10.

Publication types

Case Reports

MeSH terms

Apoptosis Regulatory Proteins / genetics
Hemangioma, Cavernous, Central Nervous System* / genetics
Humans
KRIT1 Protein / genetics
Membrane Proteins / genetics
Meningioma / genetics
Mutation* / genetics
Proto-Oncogene Proteins / genetics

Substances

Apoptosis Regulatory Proteins
KRIT1 Protein
KRIT1 protein, human
Membrane Proteins
PDCD10 protein, human
Proto-Oncogene Proteins

Supplementary concepts

Familial cerebral cavernous malformation