Journal article
K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity
N Mokbel, B Ilkovski, M Kreissl, M Memo, CM Jeffries, M Marttila, VL Lehtokari, E Lemola, M Grönholm, N Yang, D Menard, P Marcorelles, A Echaniz-Laguna, J Reimann, M Vainzof, N Monnier, G Ravenscroft, E McNamara, KJ Nowak, NG Laing Show all
Brain | Published : 2013
DOI: 10.1093/brain/aws348
Abstract
Mutations in the TPM2 gene, which encodes β-tropomyosin, are an established cause of several congenital skeletal myopathies and distal arthrogryposis. We have identified a TPM2 mutation, p.K7del, in five unrelated families with nemaline myopathy and a consistent distinctive clinical phenotype. Patients develop large joint contractures during childhood, followed by slowly progressive skeletal muscle weakness during adulthood. The TPM2 p.K7del mutation results in the loss of a highly conserved lysine residue near the N-terminus of β-tropomyosin, which is predicted to disrupt head-to-tail polymerization of tropomyosin. Recombinant K7del-β-tropomyosin incorporates poorly into sarcomeres in C2C12..
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Awarded by Australian Research Council
Funding Acknowledgements
National Health and Medical Research Council of Australia [571287 (to N.C.), 403941 (to K.N.N.), 1022707 (to K.N.N. and N.C.) and 1002147 (to N.L.)], a Foundation Building Strength for Nemaline Myopathy grant (2009; to B.I., K.N.N. and N.C.) a VENI grant from the Dutch Organization for Scientific Research, the seventh Framework Program of the European Union [project "NEMMYOP" (to C.O.)], the Australian Academy of Science (to G. R.), Australian Research Council Future Fellowship [FT100100734 (to K.J.N.)] and an Endeavour international postgraduate research scholarship (EIPRS) from the University of Sydney (to N.M.).