First Report of Concomitant Pathogenic Mutations Within MGC4607/CCM2 and KRIT1/CCM1 in a Familial Cerebral Cavernous Malformation Patient
| Autor: | Fabrícia Lima Fontes-Dantas, Gustavo da Fontoura Galvão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Elielson Veloso da Silva, Ricardo Castro de Oliveira Filho |
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| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.diagnostic_test business.industry media_common.quotation_subject Nonsense Central nervous system Magnetic resonance imaging medicine.disease Phenotype Frameshift mutation 03 medical and health sciences Epilepsy 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Concomitant medicine Surgery Neurology (clinical) business Gene 030217 neurology & neurosurgery media_common |
| Zdroj: | World Neurosurgery. 142:481-486.e1 |
| ISSN: | 1878-8750 |
| DOI: | 10.1016/j.wneu.2020.06.170 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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