Hereditary myopathy with early respiratory failure: Occurrence in various populations

Johanna Palmio, Anni Evilä, Françoise Chapon, Giorgio Tasca, Fengqing Xiang, Björn Bradvik, Bruno Eymard, Andoni Echaniz-Laguna, Jocelyn Laporte, Mikko Kärppä, Ibrahim Mahjneh, Rosaline Quinlivan, Pascal Laforêt, Maxwell Damian, Andres Berardo, Ana Lia Taratuto, Jose Antonio Bueri, Johanna Tommiska, Taneli Raivio, Matthias TuerkPhilipp Gölitz, Frederic Chevessier, Caroline Sewry, Fiona Norwood, Carola Hedberg, Rolf Schröder, Lars Edström, Anders Oldfors, Peter Hackman, Bjarne Udd

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume85
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Connectin
Mutation
Population
Respiratory Insufficiency
Exons
Exome
Biopsy
Muscles
Inheritance Patterns
Molecular Epidemiology
Muscle Weakness
Muscular Diseases
Hereditary Myopathy with Early Respiratory Failure
Molecular Biology
Parents
Phenotype
DNA
Proteins
Causes
Sequencing

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

Cite this

Hereditary myopathy with early respiratory failure : Occurrence in various populations. / Palmio, Johanna; Evilä, Anni; Chapon, Françoise; Tasca, Giorgio; Xiang, Fengqing; Bradvik, Björn; Eymard, Bruno; Echaniz-Laguna, Andoni; Laporte, Jocelyn; Kärppä, Mikko; Mahjneh, Ibrahim; Quinlivan, Rosaline; Laforêt, Pascal; Damian, Maxwell; Berardo, Andres; Taratuto, Ana Lia; Bueri, Jose Antonio; Tommiska, Johanna; Raivio, Taneli; Tuerk, Matthias; Gölitz, Philipp; Chevessier, Frederic; Sewry, Caroline; Norwood, Fiona; Hedberg, Carola; Schröder, Rolf; Edström, Lars; Oldfors, Anders; Hackman, Peter; Udd, Bjarne.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 85, No. 3, 03.2014, p. 345-353.

Research output: Contribution to journalArticle

Palmio, J, Evilä, A, Chapon, F, Tasca, G, Xiang, F, Bradvik, B, Eymard, B, Echaniz-Laguna, A, Laporte, J, Kärppä, M, Mahjneh, I, Quinlivan, R, Laforêt, P, Damian, M, Berardo, A, Taratuto, AL, Bueri, JA, Tommiska, J, Raivio, T, Tuerk, M, Gölitz, P, Chevessier, F, Sewry, C, Norwood, F, Hedberg, C, Schröder, R, Edström, L, Oldfors, A, Hackman, P & Udd, B 2014, 'Hereditary myopathy with early respiratory failure: Occurrence in various populations', Journal of Neurology, Neurosurgery and Psychiatry, vol. 85, no. 3, pp. 345-353. https://doi.org/10.1136/jnnp-2013-304965
Palmio, Johanna ; Evilä, Anni ; Chapon, Françoise ; Tasca, Giorgio ; Xiang, Fengqing ; Bradvik, Björn ; Eymard, Bruno ; Echaniz-Laguna, Andoni ; Laporte, Jocelyn ; Kärppä, Mikko ; Mahjneh, Ibrahim ; Quinlivan, Rosaline ; Laforêt, Pascal ; Damian, Maxwell ; Berardo, Andres ; Taratuto, Ana Lia ; Bueri, Jose Antonio ; Tommiska, Johanna ; Raivio, Taneli ; Tuerk, Matthias ; Gölitz, Philipp ; Chevessier, Frederic ; Sewry, Caroline ; Norwood, Fiona ; Hedberg, Carola ; Schröder, Rolf ; Edström, Lars ; Oldfors, Anders ; Hackman, Peter ; Udd, Bjarne. / Hereditary myopathy with early respiratory failure : Occurrence in various populations. In: Journal of Neurology, Neurosurgery and Psychiatry. 2014 ; Vol. 85, No. 3. pp. 345-353.
@article{ea974738aad348bf8a2d8703bc899b6d,
title = "Hereditary myopathy with early respiratory failure: Occurrence in various populations",
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 = "Johanna Palmio and Anni Evil{\"a} and Fran{\cc}oise Chapon and Giorgio Tasca and Fengqing Xiang and Bj{\"o}rn Bradvik and Bruno Eymard and Andoni Echaniz-Laguna and Jocelyn Laporte and Mikko K{\"a}rpp{\"a} and Ibrahim Mahjneh and Rosaline Quinlivan and Pascal Lafor{\^e}t and Maxwell Damian and Andres Berardo and Taratuto, {Ana Lia} and Bueri, {Jose Antonio} and Johanna Tommiska and Taneli Raivio and Matthias Tuerk and Philipp G{\"o}litz and Frederic Chevessier and Caroline Sewry and Fiona Norwood and Carola Hedberg and Rolf Schr{\"o}der and Lars Edstr{\"o}m and Anders Oldfors and Peter Hackman and Bjarne Udd",
year = "2014",
month = "3",
doi = "10.1136/jnnp-2013-304965",
language = "English",
volume = "85",
pages = "345--353",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - Hereditary myopathy with early respiratory failure

T2 - Occurrence in various populations

AU - Palmio, Johanna

AU - Evilä, Anni

AU - Chapon, Françoise

AU - Tasca, Giorgio

AU - Xiang, Fengqing

AU - Bradvik, Björn

AU - Eymard, Bruno

AU - Echaniz-Laguna, Andoni

AU - Laporte, Jocelyn

AU - Kärppä, Mikko

AU - Mahjneh, Ibrahim

AU - Quinlivan, Rosaline

AU - Laforêt, Pascal

AU - Damian, Maxwell

AU - Berardo, Andres

AU - Taratuto, Ana Lia

AU - Bueri, Jose Antonio

AU - Tommiska, Johanna

AU - Raivio, Taneli

AU - Tuerk, Matthias

AU - Gölitz, Philipp

AU - Chevessier, Frederic

AU - Sewry, Caroline

AU - Norwood, Fiona

AU - Hedberg, Carola

AU - Schröder, Rolf

AU - Edström, Lars

AU - Oldfors, Anders

AU - Hackman, Peter

AU - Udd, Bjarne

PY - 2014/3

Y1 - 2014/3

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84896740436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896740436&partnerID=8YFLogxK

U2 - 10.1136/jnnp-2013-304965

DO - 10.1136/jnnp-2013-304965

M3 - Article

C2 - 23606733

AN - SCOPUS:84896740436

VL - 85

SP - 345

EP - 353

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 3

ER -