Next-generation sequencing approach to hyperCKemia
| Autor: | Simona Salvatore, Nila Volpi, Michele Sacchini, Paola Tonin, Federico Melani, Filippo M. Santorelli, Giulia Bertocci, M. Alice Donati, Sara Lenzi, M. Teresa Dotti, Gabriele Siciliano, Anna Rubegni, Salvatore Grosso, Claudia Dosi, Deborah Tolomeo, Carla Battisti, Fabio Giannini, Guja Astrea, Renzo Guerrini, Jacopo Baldacci, Alessandro Malandrini, Antonio Federico, Denise Cassandrini, Maria Antonietta Maioli, Eugenio Mercuri |
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| Rok vydání: | 2019 |
| Předmět: |
myalgia
Pediatrics medicine.medical_specialty Proximal muscle weakness GIRDLE MUSCULAR-DYSTROPHIES MOLECULAR DIAGNOSIS Asymptomatic RYR1 MUTATIONS DISEASE NORTH-AMERICAN medicine MALIGNANT HYPERTHERMIA RYANODINE RECEPTOR MUSCLE BIOPSY IDENTIFICATION GENE Genetics (clinical) Muscle biopsy medicine.diagnostic_test Genetic heterogeneity business.industry medicine.disease Distal Myopathies Neurology (clinical) medicine.symptom business Rhabdomyolysis Cohort study |
| Zdroj: | Neurology Genetics. 5:e352 |
| ISSN: | 2376-7839 |
| DOI: | 10.1212/nxg.0000000000000352 |
| Popis: | ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance. |
| Databáze: | OpenAIRE |
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