Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 May 2024
20 May 2024
Historique:
received:
15
10
2023
accepted:
03
05
2024
medline:
21
5
2024
pubmed:
21
5
2024
entrez:
20
5
2024
Statut:
epublish
Résumé
Hypomyelinating leukodystrophy (HLD) is an autosomal recessive disorder characterized by defective central nervous system myelination. Exome sequencing of two siblings with severe cognitive and motor impairment and progressive hypomyelination characteristic of HLD revealed homozygosity for a missense single-nucleotide variant (SNV) in EPRS1 (c.4444 C > A; p.Pro1482Thr), encoding glutamyl-prolyl-tRNA synthetase, consistent with HLD15. Patient lymphoblastoid cell lines express markedly reduced EPRS1 protein due to dual defects in nuclear export and cytoplasmic translation of variant EPRS1 mRNA. Variant mRNA exhibits reduced METTL3 methyltransferase-mediated writing of N
Identifiants
pubmed: 38769304
doi: 10.1038/s41467-024-48549-x
pii: 10.1038/s41467-024-48549-x
doi:
Substances chimiques
N-methyladenosine
0
METTL3 protein, human
0
YTHDC1 protein, human
0
YTHDF1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4284Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK124203
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130377
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067146
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS124547
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS124581
Pays : United States
Informations de copyright
© 2024. The Author(s).
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