Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy - Archive ouverte HAL Access content directly
Journal Articles Human Mutation Year : 2012

Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

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Elizabeth T Dechene
  • Function : Author
Marc Bitoun
Christophe Pierson
  • Function : Author
Melissa A Dempsey
  • Function : Author
Fabrice Klein
  • Function : Author
Nicolas Dondaine
  • Function : Author
Nicolas Haumesser
  • Function : Author
Claire Poirson
  • Function : Author
Rebecca S Greenleaf
  • Function : Author
Melissa A Barger
  • Function : Author
Lane J Mahoney
  • Function : Author
Peter B Kang
  • Function : Author
Edmar Zanoteli
  • Function : Author
Nanna Witting
  • Function : Author
Andoni Echaniz-Laguna
James J. Dowling
  • Function : Author
  • PersonId : 933901
Luciano Merlini
  • Function : Author
CNR
Anders Oldfors
  • Function : Author
Lilian Bomme Ousager
  • Function : Author
Judith Melki
  • Function : Author
  • PersonId : 931056
Acary S B Oliveira
  • Function : Author
David Mowat
  • Function : Author
Michele Michel
  • Function : Author
Juan José Poza Aldea
  • Function : Author
Fabrice Michel
  • Function : Author
  • PersonId : 758089
  • IdRef : 17879337X
Jose E Barcena Llona
  • Function : Author
Jon Andoni Urtizberea
  • Function : Author
Bernard Prudhon
Melanie Bedford
  • Function : Author
Katherine Mathews
  • Function : Author
Lori a H Erby
  • Function : Author
Stephen A Smith
  • Function : Author
Jennifer Roggenbuck
  • Function : Author
Carol A Crowe
  • Function : Author
  • PersonId : 906270
Allison Brennan Spitale
  • Function : Author
Sheila C Johal
  • Function : Author
Anthony A Amato
  • Function : Author
Laurie A Demmer
  • Function : Author
Jessica Jonas
  • Function : Author
Basil T Darras
  • Function : Author
Thomas D Bird
  • Function : Author
Mercy Laurino
  • Function : Author
Selman I Welt
  • Function : Author
Cynthia Trotter
  • Function : Author
Pascale Guicheney
  • Function : Author
  • PersonId : 905805
Alan H Beggs
  • Function : Author
Elizabeth T. Dechene
  • Function : Author
Melissa A. Dempsey
  • Function : Author
Rebecca S. Greenleaf
  • Function : Author
Melissa A. Barger
  • Function : Author
Lane J. Mahoney
  • Function : Author
Peter B. Kang
  • Function : Author
Acary S. B. Oliveira
  • Function : Author
Jose E. Barcena Llona
  • Function : Author
Lori A. H. Erby
  • Function : Author
Stephen A. Smith
  • Function : Author
Carol A. Crowe
  • Function : Author
Sheila C. Johal
  • Function : Author
Anthony A. Amato
  • Function : Author
Laurie A. Demmer
  • Function : Author
Basil T. Darras
  • Function : Author
Thomas D. Bird
  • Function : Author
Selman I. Welt
  • Function : Author

Abstract

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.

Dates and versions

hal-01681807 , version 1 (11-01-2018)

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Cite

Johann Böhm, Valérie Biancalana, Elizabeth T Dechene, Marc Bitoun, Christophe Pierson, et al.. Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. Human Mutation, 2012, 33 (6), pp.949 - 959. ⟨10.1002/humu.22067⟩. ⟨hal-01681807⟩
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