End-Truncated LAMB1 Causes a Hippocampal Memory Defect and a Leukoencephalopathy.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
01
10
2021
received:
18
03
2021
accepted:
02
10
2021
pubmed:
5
10
2021
medline:
15
12
2021
entrez:
4
10
2021
Statut:
ppublish
Résumé
The majority of patients with a familial cerebral small vessel disease (CSVD) referred for molecular screening do not show pathogenic variants in known genes. In this study, we aimed to identify novel CSVD causal genes. We performed a gene-based collapsing test of rare protein-truncating variants identified in exome data of 258 unrelated CSVD patients of an ethnically matched control cohort and of 2 publicly available large-scale databases, gnomAD and TOPMed. Western blotting was used to investigate the functional consequences of variants. Clinical and magnetic resonance imaging features of mutated patients were characterized. We showed that LAMB1 truncating variants escaping nonsense-mediated messenger RNA decay are strongly overrepresented in CSVD patients, reaching genome-wide significance (p < 5 × 10 These findings are important for diagnosis and clinical care, to avoid unnecessary and sometimes invasive investigations, and also from a mechanistic point of view to understand the role of extracellular matrix proteins in neuronal homeostasis. ANN NEUROL 2021;90:962-975.
Substances chimiques
LAMB1 protein, human
0
Laminin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
962-975Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-16-RHUS- 0004
Informations de copyright
© 2021 American Neurological Association.
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