Introduction: Hereditary inclusion body myopathy (hIBM) refers to a group of clinically and genetically heterogeneous diseases. The overlapping histochemical features of hIBM with other genetic disorders lead to low diagnostic rates with targeted single-gene sequencing. This is true for the most prevalent form of hIBM, GNEpathy. Therefore, we used whole-exome sequencing (WES) to determine whether a cohort of clinically suspected GNEpathy patients undiagnosed by targeted GNE analysis could be genetically characterized.
Methods: Twenty patients with hIBM but undiagnosed by targeted GNE sequencing were analyzed by WES before data filtering on 306 genes associated with neuromuscular disorders.
Results: Seven patients out of 20 were found to have disease-causing mutations in genes associated with hIBM or genes allowing for hIBM in the differential diagnosis or associated with unexpected diagnosis.
Discussion: Next-generation sequencing is an efficient strategy in the context of hIBM, resulting in a molecular diagnosis for 35% of the patients initially undiagnosed by targeted GNE analysis. Muscle Nerve 56: 993-997, 2017.
Keywords: GNE; NGS; diagnosis; exome; hIBM; myopathy.
© 2017 Wiley Periodicals, Inc.