Abstract
Laing early-onset distal myopathy is a rare autosomal dominant myopathy and caused by mutations in the MYH7 gene, encoding the slow beta myosin heavy chain. We report the first molecularly verified Laing distal myopathy in a French family caused by a novel p.Glu1508del mutation in the MYH7 gene. Interestingly, we identified the identical mutation in an unrelated Norwegian family and, as a de novo mutation, in one sporadic Finnish patient. Described in detail are the clinical and electrophysiological characteristics of 5 patients from the French family. The phenotype in the Finnish patient and the Norwegian patients is largely similar. This mutation causes a benign myopathy within the range of previously reported Laing myopathy phenotype variations. Onset of weakness in the tibialis anterior (TA) muscles occurred in early childhood in all patients. Finger extensor and neck flexor weakness together with Achilles tendon retractions were other frequent findings. The independent recurrence of the identical mutation without any founder background may reflect a mutational susceptibility of this residue, in accordance with some other MYH7 mutations previously reported. De novo mutations seem to be frequent in Laing distal myopathy. This is of clinical importance since a dominant family history is missing, which may confuse differential diagnostic efforts.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Udd B (2007) Distal myopathies. In: Hilton-Jones D, Mastaglia F (eds) Clinical handbook of neurology 3rd edition, Volume: myopathies and muscle diseases. Elsevier, Amsterdam pp 215–242
Laing NG, Laing BA, Meredith C, Wilton SD, Robbins P, Honeyman K, Dorosz S, Kozman H, Mastaglia FL, Kakulas BA (1995) Autosomal dominant distal myopathy: linkage to chromosome 14. Am J Hum Genet 56:422–427
Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, Durling HJ, Duff RM, Beckman K, de Visser M, van der Graaff MM, Hedera P, Fink JK, Petty EM, Lamont P, Fabian V, Bridges L, Voit T, Mastaglia FL, Laing NG (2004) Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet 75:703–708
Lamont PJ, Udd B, Mastaglia FL, de Visser M, Hedera P, Voit T, Bridges LR, Fabian V, Rozemuller A, Laing NG (2006) Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy. J Neurol Neurosurg Psychiatry 77:208–215
Viala K, Renié L, Maisonobe T, Béhin A, Neil J, Leger JM, Bouche P (2004) Follow-up study and response to treatment in 23 patients with Lewis-Sumner syndrome. Brain 127:2010–2017
Wallgren-Pettersson C, Lehtokari V-L, Kalimo H, Paetau A, Nuutinen E, Hackman P, Sewry C, Pelin K, Udd B (2007) Distal myopathy caused by homozygous missense mutations in the nebulin gene. Brain 130:1465–1476
Raheem O, Huovinen S, Haapasalo H, Udd B (2010) Novel myosin heavy chain immunohistochemical double staining developed for the routine diagnostic separation of I, IIA and IIX fibers. Acta Neuropathol 119:495–500
Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG (1990) A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 62:999–1006
Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE (2000) Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med 343:1688–1696
Tajsharghi H, Thornell LE, Lindberg C, Lindvall B, Henriksson KG, Oldfors A (2003) Myosin storage myopathy associated with a heterozygous missense mutation in MYH7. Ann Neurol 54:494–500
Bohlega S, Abu-Amero SN, Wakil SM, Carroll P, Al-Amr R, Lach B, Al-Sayed Y, Cupler EJ, Meyer BF (2004) Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy. Neurology 62:1518–1521
Mastaglia FL, Phillips BA, Cala LA, Meredith C, Egli S, Akkari PA, Laing NG (2002) Early onset chromosome 14-linked distal myopathy (Laing). Neuromuscul Disord 12:350–357
Hedera P, Petty EM, Bui MR, Blaivas M, Fink JK (2003) The second kindred with autosomal dominant distal myopathy linked to chromosome 14q: genetic and clinical analysis. Arch Neurol 60:1321–1325
Muelas N, Hackman P, Luque H, Garcés-Sánchez M, Azorín I, Suominen T, Sevilla T, Mayordomo F, Gómez L, Martí P, María Millán J, Udd B, Vílchez JJ (2010) MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy. Neurology 75:732–741
Overeem S, Schelhaas HJ, Blijham PJ, Grootscholten MI, ter Laak HJ, Timmermans J, van den Wijngaard A, Zwarts MJ (2007) Symptomatic distal myopathy with cardiomyopathy due to a MYH7 mutation. Neuromuscul Disord 17:490–493
Béhin A, Dubourg O, Laforêt P, Pêcheux C, Bernard R, Lévy N, Eymard B (2008) [Distal myopathy due to mutations of GNE gene: clinical spectrum and diagnosis]. Rev Neurol (Paris) 164:434–443
Zimprich F, Djamshidian A, Hainfellner JA, Budka H, Zeitlhofer J (2000) An autosomal dominant early adult-onset distal muscular dystrophy. Muscle Nerve 23:1876–1879
Mastaglia FL, Laing NG (1996) Investigation of muscle disease. J Neurol Neurosurg Psychiatry 60:256–274
Voit T, Kutz P, Leube B, Neuen-Jacob E, Schröder JM, Cavallotti D, Vaccario ML, Schaper J, Broich P, Cohn R, Baethmann M, Göhlich-Ratmann G, Scoppetta C, Herrmann R (2001) Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus. Neuromuscul Disord 11:11–19
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dubourg, O., Maisonobe, T., Behin, A. et al. A novel MYH7 mutation occurring independently in French and Norwegian Laing distal myopathy families and de novo in one Finnish patient. J Neurol 258, 1157–1163 (2011). https://doi.org/10.1007/s00415-011-5900-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-011-5900-9