Abstract
Pathogenic HNRNPA1 variants underlying myopathy have been reported only in the prion-like domain of the heterogenous nuclear ribonucleoproteins A1, while two variants in the nuclear localization (PY-NLS) domain were described in ALS. Here we report a 61-year-old man who presented with 1-year history of bilateral foot drop without Paget disease or dementia. Examination revealed severe asymmetric distal weakness, predominantly affecting tibialis anterior and toe extensors. Creatine kinase was 1,013 U/L (normal <308). Alkaline phosphatase was normal. EMG demonstrated small polyphasic motor unit potentials and fibrillation potentials. Muscle biopsy showed numerous fibers containing rimmed vacuoles and occasional fibers harboring congophilic inclusions, or p62/TDP-43/hnRNPA1-immunoreacted aggregates. Next generation sequencing identified a novel heterozygous (c.959A>T, p. Asn320Ile) variant in HNRNPA1, affecting a highly conserved amino acid in PY-NLS domain. Muscle MRI showed abnormalities, consistent with HNRNPA1-myopathy. This patient expands the phenotypic spectrum of hnRNPA1-opathy due to a PY-NLS domain variant to include isolated distal myopathy.
Original language | English (US) |
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Pages (from-to) | 521-526 |
Number of pages | 6 |
Journal | Neuromuscular Disorders |
Volume | 32 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2022 |
Keywords
- Distal myopathy
- Hnrnpa1
- Inclusion body myopathy
- Multisystem proteinopathy
- Nuclear localization sequence
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Neurology
- Clinical Neurology
- Genetics(clinical)