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Hereditary myopathy with early respiratory failure: occurrence in various populations

Palmio, Johanna; Evila, Anni; Chapon, Francoise; Tasca, Giorgio; Xiang, Fengqing; Brådvik, Björn LU ; Eymard, Bruno; Echaniz-Laguna, Andoni; Laporte, Jocelyn and Karppa, Mikko, et al. (2014) In Journal of Neurology, Neurosurgery and Psychiatry 85(3). p.345-353
Abstract
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... (More)
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. (Less)
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published
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keywords
EPIDEMIOLOGY, GENETICS, MYOPATHY
in
Journal of Neurology, Neurosurgery and Psychiatry
volume
85
issue
3
pages
345 - 353
publisher
BMJ Publishing Group
external identifiers
  • wos:000331268600022
  • scopus:84896740436
ISSN
1468-330X
DOI
10.1136/jnnp-2013-304965
language
English
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yes
id
98cbe5b5-00b6-4b66-8469-9b407c7bf3f3 (old id 4417638)
date added to LUP
2014-05-05 07:21:10
date last changed
2017-11-05 03:59:05
@article{98cbe5b5-00b6-4b66-8469-9b407c7bf3f3,
  abstract     = {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.},
  author       = {Palmio, Johanna and Evila, Anni and Chapon, Francoise and Tasca, Giorgio and Xiang, Fengqing and Brådvik, Björn and Eymard, Bruno and Echaniz-Laguna, Andoni and Laporte, Jocelyn and Karppa, Mikko and Mahjneh, Ibrahim and Quinlivan, Rosaline and Laforet, Pascal and Damian, Maxwell and Berardo, Andres and Taratuto, Ana Lia and Bueri, Jose Antonio and Tommiska, Johanna and Raivio, Taneli and Tuerk, Matthias and Goelitz, Philipp and Chevessier, Frederic and Sewry, Caroline and Norwood, Fiona and Hedberg, Carola and Schroeder, Rolf and Edstrom, Lars and Oldfors, Anders and Hackman, Peter and Udd, Bjarne},
  issn         = {1468-330X},
  keyword      = {EPIDEMIOLOGY,GENETICS,MYOPATHY},
  language     = {eng},
  number       = {3},
  pages        = {345--353},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Neurology, Neurosurgery and Psychiatry},
  title        = {Hereditary myopathy with early respiratory failure: occurrence in various populations},
  url          = {http://dx.doi.org/10.1136/jnnp-2013-304965},
  volume       = {85},
  year         = {2014},
}