High prevalence of sporadic late-onset nemaline myopathy in a cohort of whole-exome sequencing negative myopathy patients
| Autor: | Jonathan Baets, Willem De Ridder, Peter De Jonghe, Volker Straub |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Late onset Myopathies Nemaline Monoclonal Gammopathy of Undetermined Significance Proof of Concept Study Cohort Studies 03 medical and health sciences 0302 clinical medicine Nemaline myopathy Exome Sequencing Prevalence Humans Medicine Muscle Skeletal Myopathy Genetics (clinical) Exome sequencing Aged Muscle Weakness Muscle biopsy medicine.diagnostic_test business.industry Muscle weakness Middle Aged medicine.disease Magnetic Resonance Imaging 030104 developmental biology Neurology Pediatrics Perinatology and Child Health Cohort Immunohistochemistry Female Human medicine Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscul Disord Neuromuscular disorders |
| ISSN: | 0960-8966 |
| DOI: | 10.1016/j.nmd.2021.04.010 |
| Popis: | Sporadic late-onset nemaline myopathy (SLONM) is an enigmatic, supposedly very rare, putatively immune-mediated late-onset myopathy, typically presenting with subacutely progressive limb-girdle muscular weakness, yet slowly progressing cases have been described too. We systematically studied (para)clinical and histopathological findings in a cohort of 18 isolated yet suspected inherited myopathy patients, showing late-onset, slowly progressive limb-girdle muscle weakness, remaining unsolved after whole-exome sequencing. The presence of a monoclonal gammopathy of unknown significance (MGUS) and anti-HMGCR antibodies was determined. Biopsies were systematically re-evaluated and systematic immunohistochemical and electron microscopy studies were performed to particularly evaluate the presence of rods and/or inflammatory features. Ten patients showed rods as core feature on muscle biopsy on re-evaluation, four of these had an IgG κ MGUS in blood. As such, these ten patients represented suspected slowly progressing SLONM patients, with auxiliary data supporting this diagnosis: 1) additional muscle biopsy features pointing towards Z-disk and myofibrillar pathology; 2) a common selective pattern of muscle involvement on MRI; 3) inflammatory features on muscle biopsy. Findings in this proof-of-concept study highlight difficulties in reliably diagnosing slowly progressing SLONM and the probably underestimated prevalence of this entity in cohorts of whole exome sequencing negative myopathy patients, initially considered having an inherited myopathy. |
| Databáze: | OpenAIRE |
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