De novo exonic mutation in MYH7 gene leading to exon skipping in a patient with early onset muscular weakness and fiber-type disproportion

Abstract Here we report on a case of MYH7-related myopathyin a boy with early onset of muscular weaknessand delayed motor development in infancy. His most affected muscles were neck extensors showing a dropped head sign, proximal muscles of lower limbs with positive Gower's sign, and trunk muscles. Brain and spinal cord MRI scans, echocardiography, and laboratory analyses including creatine kinaseand lactate did not reveal any abnormalities. Muscle histopathology showed fiber-type disproportion. Whole exome sequencingof the parents-offspring trio revealed a novel de novo c.5655G>A p.(Ala1885=) synonymous substitutionof the last nucleotide in exon 38 of the MYH7gene. Further RNA investigations proved the skipping of exon 38 (p.1854_1885del). This is a first report of an exon-skippingmutation in the MYH7gene causing myopathy. This report broadens both the phenotypic and genotypic spectra of MYH7-related myopathies.