Expanded phenotype of AARS1-related white matter disease.
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
04
04
2021
accepted:
09
07
2021
revised:
08
07
2021
pubmed:
28
8
2021
medline:
23
3
2022
entrez:
27
8
2021
Statut:
ppublish
Résumé
Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease. A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts. We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes. We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.
Identifiants
pubmed: 34446925
doi: 10.1038/s41436-021-01286-8
pii: S1098-3600(21)05440-X
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2352-2359Subventions
Organisme : CIHR
ID : 201610PJT-377869
Pays : Canada
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.
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