Hereditary myopathy with early respiratory failure: occurrence in various populations

Palmio J, Evila A, Chapon F, Tasca G, Xiang F, Bradvik B, Eymard B, Echaniz-Laguna A, Laporte J, Karppa M, Mahjneh I, Quinlivan R, Laforet P, Damian M, Berardo A, Taratuto AL, Bueri JA, Tommiska J, Raivio T, Türk M, Gölitz P, Chevessier F, Sewry C, Norwood F, Hedberg C, Schröder R, Edstrom L, Oldfors A, Hackman P, Udd B (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Journal of Neurology Neurosurgery and Psychiatry BMJ Publishing Group

Publisher: BMJ Publishing Group

Book Volume: 85

Pages Range: 345-53

Journal Issue: 3

DOI: 10.1136/jnnp-2013-304965

Abstract

Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort.DNA samples of all currently known families with HMERF without molecular genetic cause were obtained from 12 families in seven different countries. Clinical, histopathological and muscle imaging data were collected and five biopsy samples made available for further immunohistochemical studies. Genotyping, exome sequencing and Sanger sequencing were used to identify and confirm sequence variations.All patients with clinical diagnosis of HMERF were genetically solved by five different titin mutations identified. One mutation has been reported while four are novel, all located exclusively in the FN3 119 domain (A150) of A-band titin. One of the new mutations showed semirecessive inheritance pattern with subclinical myopathy in the heterozygous parents. Typical clinical features were respiratory failure at mid-adulthood in an ambulant patient with very variable degree of muscle weakness. Cytoplasmic bodies were retrospectively observed in all muscle biopsy samples and these were reactive for myofibrillar proteins but not for titin.We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.

Authors with CRIS profile

Matthias Türk Lehrstuhl für Neuropathologie Philipp Gölitz Medizinische Fakultät Rolf Schröder Professur für Neuropathologie

Involved external institutions

Helsingin yliopisto / University of Helsinki FI Finland (FI) University of Gothenburg / Göteborgs universitet SE Sweden (SE) University of Tampere (UTA) / Tampereen yliopisto (Tay) FI Finland (FI) Centre Hospitalier Universitaire de Caen FR France (FR) RCCS Fondazione Don Carlo Gnocchi Onlus IT Italy (IT) Karolinska Institute SE Sweden (SE) Lund University / Lunds universitet SE Sweden (SE) University of Pittsburgh Medical Center (UPMC) US United States (USA) (US) Université de Strasbourg (UDS) FR France (FR) Oulun Yliopisto / University of Oulo FI Finland (FI) Cambridge University Hospital GB United Kingdom (GB) Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) AR Argentina (AR) Robert Jones and Agnes Hunt Orthopaedic Hospital (RJAH) GB United Kingdom (GB) King's College Hospital (KCH) GB United Kingdom (GB)

How to cite

APA:

Palmio, J., Evila, A., Chapon, F., Tasca, G., Xiang, F., Bradvik, B.,... Udd, B. (2014). Hereditary myopathy with early respiratory failure: occurrence in various populations. Journal of Neurology Neurosurgery and Psychiatry, 85(3), 345-53. https://doi.org/10.1136/jnnp-2013-304965

MLA:

Palmio, Johanna, et al. "Hereditary myopathy with early respiratory failure: occurrence in various populations." Journal of Neurology Neurosurgery and Psychiatry 85.3 (2014): 345-53.

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