First Report of Concomitant Pathogenic Mutations Within MGC4607/CCM2 and KRIT1/CCM1 in a Familial Cerebral Cavernous Malformation Patient.

Carrier Proteins / genetics Drug Resistant Epilepsy / etiology Hemangioma, Cavernous, Central Nervous System / complications Humans KRIT1 Protein / genetics Magnetic Resonance Imaging Middle Aged
CCM1 (KRIT1) CCM2 (MGC4607) Cerebral cavernous malformation Epilepsy

Journal

World neurosurgery
ISSN: 1878-8769
Titre abrégé: World Neurosurg
Pays: United States
ID NLM: 101528275

Informations de publication

Date de publication:
10 2020
Historique:
received: 21 05 2020
revised: 18 06 2020
accepted: 21 06 2020
pubmed: 3 7 2020
medline: 15 1 2021
entrez: 3 7 2020
Statut: ppublish

Résumé

Familial cerebral cavernous malformations (CCM) are among the most common vascular malformations of the central nervous system (CNS) and are linked to mutations on the specific genes CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. We present the first report in the literature of a pharmaco-resistant epileptic patient harboring co-occurring pathogenic mutations within CCM2/MGC4607 and CCM1/KRIT1. A 51-year-old patient first presented at age of 33 years with episodes of seizures. Magnetic resonance imaging including a susceptibility-weighted imaging sequence had shown multiple cerebral cavernous malformation lesions. She had partial response of symptoms and remained in routine follow-up needing progressive pharmacological improvement. Direct sequencing allowed the detection of 1 nonsense pathogenic mutation in CCM2/MGC4607 (c.118C>T; p.Arg40Ter) and 1 unclassified frameshift insertion variant in CCM1/KRIT1 (c.1687_1688insT; p.Tyr563LeufsTer5). Although the CCM2/MGC460 variant seems to be the major contributor for the patient's CCM phenotype, the mutated CCM1/KRIT1 seems to act as a booster to CCM overall pathogenicity.

Sections du résumé

BACKGROUND
Familial cerebral cavernous malformations (CCM) are among the most common vascular malformations of the central nervous system (CNS) and are linked to mutations on the specific genes CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. We present the first report in the literature of a pharmaco-resistant epileptic patient harboring co-occurring pathogenic mutations within CCM2/MGC4607 and CCM1/KRIT1.
CASE DESCRIPTION
A 51-year-old patient first presented at age of 33 years with episodes of seizures. Magnetic resonance imaging including a susceptibility-weighted imaging sequence had shown multiple cerebral cavernous malformation lesions. She had partial response of symptoms and remained in routine follow-up needing progressive pharmacological improvement. Direct sequencing allowed the detection of 1 nonsense pathogenic mutation in CCM2/MGC4607 (c.118C>T; p.Arg40Ter) and 1 unclassified frameshift insertion variant in CCM1/KRIT1 (c.1687_1688insT; p.Tyr563LeufsTer5).
CONCLUSIONS
Although the CCM2/MGC460 variant seems to be the major contributor for the patient's CCM phenotype, the mutated CCM1/KRIT1 seems to act as a booster to CCM overall pathogenicity.

Identifiants

DOI: 10.1016/j.wneu.2020.06.170 PMID: 32615293
pubmed: 32615293
pii: S1878-8750(20)31438-8
doi: 10.1016/j.wneu.2020.06.170
pii:
doi:

Substances chimiques

CCM2 protein, human 0
Carrier Proteins 0
KRIT1 Protein 0
KRIT1 protein, human 0

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

481-486.e1

Informations de copyright

Copyright © 2020. Published by Elsevier Inc.

Auteurs

Gustavo da Fontoura Galvão (G)

Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurosurgery, Rio de Janeiro RJ, Brazil; Federal University of the State of Rio de Janeiro, Translational Neuroscience Laboratory, Post-Graduation Program in Neurology, Rio de Janeiro RJ, Brazil.

Elielson Veloso da Silva (E)

Federal University of the State of Rio de Janeiro, Translational Neuroscience Laboratory, Post-Graduation Program in Neurology, Rio de Janeiro RJ, Brazil; Fluminense Federal University, Post-Graduation Program in Neurology and Neuroscience, Rio de Janeiro RJ, Brazil.

Fabrícia Lima Fontes-Dantas (FL)

Federal University of the State of Rio de Janeiro, Translational Neuroscience Laboratory, Post-Graduation Program in Neurology, Rio de Janeiro RJ, Brazil.

Ricardo Castro Filho (RC)

Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurosurgery, Rio de Janeiro RJ, Brazil.

Soniza Alves-Leon (S)

Federal University of the State of Rio de Janeiro, Translational Neuroscience Laboratory, Post-Graduation Program in Neurology, Rio de Janeiro RJ, Brazil; Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurology, Rio de Janeiro RJ, Brazil.

Jorge Marcondes de Souza (J)

Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurosurgery, Rio de Janeiro RJ, Brazil. Electronic address: jormarcondes@gmail.com.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Épilepsie › Épilepsie pharmacorésistante › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations du système nerveux › Malformations vasculaires du système nerveux central › Hémangiome caverneux du système nerveux central › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéine KRIT1 › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › First Report of Concomitant Pathogenic...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › First Report of Concomitant Pathogenic...