RT Journal Article
SR Electronic
T1 Hereditary myopathy with early respiratory failure: occurrence in various populations
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP jnnp-2013-304965
DO 10.1136/jnnp-2013-304965
A1 Johanna Palmio
A1 Anni Evilä
A1 Françoise Chapon
A1 Giorgio Tasca
A1 Fengqing Xiang
A1 Björn Brådvik
A1 Bruno Eymard
A1 Andoni Echaniz-Laguna
A1 Jocelyn Laporte
A1 Mikko Kärppä
A1 Ibrahim Mahjneh
A1 Rosaline Quinlivan
A1 Pascal Laforêt
A1 Maxwell Damian
A1 Andres Berardo
A1 Ana Lia Taratuto
A1 Jose Antonio Bueri
A1 Johanna Tommiska
A1 Taneli Raivio
A1 Matthias Tuerk
A1 Philipp Gölitz
A1 Frederic Chevessier
A1 Caroline Sewry
A1 Fiona Norwood
A1 Carola Hedberg
A1 Rolf Schröder
A1 Lars Edström
A1 Anders Oldfors
A1 Peter Hackman
A1 Bjarne Udd
YR 2013
UL http://jnnp.bmj.com/content/early/2013/04/18/jnnp-2013-304965.abstract
AB Objective 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. Methods 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. Results 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. Conclusions 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.