A Novel Multisystem Proteinopathy Caused by a Missense ANXA11 Variant
| Autor: | Alexandre Hilário B. Mattos, Alberto R. M. Martinez, Antonio Rodrigues Coimbra Neto, Carelis González-Salazar, Fabio Rogerio, Thiago Junqueira Ribeiro de Rezende, Ana Luisa de Carvalho Cardozo Hernández, João Paulo Kitajima, Felipe Franco da Graça, Edmar Zanoteli, João Pedro Nunes Gonçalves, Alexandre Leite Rodrigues de Oliveira, Marcondes C. França, Anamarli Nucci, Lucas Mitsuo Taniguti, Fernando Kok, Tauana Bernardes Leoni, André Macedo Serafim da Silva |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Annexins Mutation Missense 03 medical and health sciences 0302 clinical medicine Ptosis Exome Sequencing medicine Humans Dementia Missense mutation Amino Acid Sequence Amyotrophic lateral sclerosis Pathological Aged Hereditary inclusion body myopathy business.industry Genetic Variation Neurodegenerative Diseases Middle Aged medicine.disease Magnetic Resonance Imaging Phenotype Pedigree Multisystem proteinopathy 030104 developmental biology Neurology Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Annals of Neurology. 90:239-252 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.26136 |
| Popis: | Objective Protein misfolding plays a central role not only in amyotrophic lateral sclerosis (ALS), but also in other conditions, such as frontemporal dementia (FTD), inclusion body myopathy (hIBM) or Paget's disease of bone. The concept of multisystem proteinopathies (MSP) was created to account for those rare families that segregate at least 2 out of these 4 conditions in the same pedigree. The calcium-dependent phospholipid-binding protein annexin A11 was recently associated to ALS in European pedigrees. Herein, we describe in detail 3 Brazilian families presenting hIBM (isolated or in combination with ALS/FTD) caused by the novel p.D40Y change in the gene encoding annexin A11 (ANXA11). Methods We collected clinical, genetic, pathological and skeletal muscle imaging from 11 affected subjects. Neuroimaging was also obtained from 8 patients and 8 matched controls. Results Clinico-radiological phenotype of this novel hIBM reveals a slowly progressive predominant limb-girdle syndrome, but with frequent axial (ptosis/dropped head) and distal (medial gastrocnemius) involvement as well. Muscle pathology identified numerous rimmed vacuoles with positive annexin A11, TDP-43 and p62 inclusions, but no inflammation. Central nervous system was also involved: two patients had FTD, but diffusion tensor imaging uncovered multiple areas of cerebral white matter damage in the whole group (including the corticospinal tracts and frontal subcortical regions). Interpretation These findings expand the phenotypic spectrum related to ANXA11. This gene should be considered the cause of a novel multisystem proteinopathy (MSP type 6), rather than just ALS. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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