title: 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 myopathy in a boy with early onset of muscular weakness and 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 kinase and lactate did not reveal any abnormalities. Muscle histopathology showed fiber-type disproportion. Whole exome sequencing of the parents-offspring trio revealed a novel de novo c.5655G>A p.(Ala1885=) synonymous substitution of the last nucleotide in exon 38 of the MYH7 gene. Further RNA investigations proved the skipping of exon 38 (p.1854_1885del). This is a first report of an exon-skipping mutation in the MYH7 gene causing myopathy. This report broadens both the phenotypic and genotypic spectra of MYH7-related myopathies.
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia. Electronic address: sander.pajusalu@kliinikum.ee.
authors.forename: Sander
authors.initials: S
authors.lastname: Pajusalu
authors.affiliation: Department of Pediatrics, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Inga
authors.initials: I
authors.lastname: Talvik
authors.affiliation: Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Klari
authors.initials: K
authors.lastname: Noormets
authors.affiliation: Department of Pediatrics, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Tiina
authors.initials: T
authors.lastname: Talvik
authors.affiliation: Tallinn Children's Hospital, Tallinn, Estonia.
authors.forename: Haide
authors.initials: H
authors.lastname: Põder
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Kairit
authors.initials: K
authors.lastname: Joost
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Sanna
authors.initials: S
authors.lastname: Puusepp
authors.affiliation: Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Piirsoo
authors.affiliation: Department of Neuropathology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.affiliation: Department of Neuropathology, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Goebel
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Tiit
authors.initials: T
authors.lastname: Nikopensius
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Tarmo
authors.initials: T
authors.lastname: Annilo
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Margit
authors.initials: M
authors.lastname: Nõukas
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Pediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Õunap
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia; Department of Pediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Reimand
mesh_terms: D024722:Cardiac Myosins / Q000235:genetics*; D005091:Exons; D006801:Humans; D007223:Infant; D008297:Male; D018908:Muscle Weakness / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics*
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Dropped head sign; Exon skipping; Fiber-type disproportion; MYH7 gene; Myopathy; Whole exome sequencing