Hereditary myopathy with early respiratory failure: occurrence in various populations

Journal article

Publication Details

Author(s): 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
Journal: Journal of Neurology Neurosurgery and Psychiatry
Publisher: BMJ Publishing Group
Publication year: 2014
Volume: 85
Journal issue: 3
Pages range: 345-53
ISSN: 0022-3050


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.

FAU Authors / FAU Editors

Gölitz, Philipp PD Dr.
Medizinische Fakultät
Schröder, Rolf Prof. Dr.
Professur für Neuropathologie
Türk, Matthias
Lehrstuhl für Neuropathologie

External institutions with authors

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

How to cite

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.

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.


Last updated on 2018-05-10 at 02:30