Artículos de revistas
Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype-Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy
Fecha
2012Registro en:
HUMAN MUTATION, MALDEN, v. 33, n. 6, Special Issue, supl. 1, Part 1, pp. 949-959, JUN, 2012
1059-7794
10.1002/humu.22067
Autor
Boehm, Johann
Biancalana, Valerie
DeChene, Elizabeth T.
Bitoun, Marc
Pierson, Christopher R.
Schaefer, Elise
Karasoy, Hatice
Dempsey, Melissa A.
Klein, Fabrice
Dondaine, Nicolas
Kretz, Christine
Haumesser, Nicolas
Poirson, Claire
Toussaint, Anne
Greenleaf, Rebecca S.
Barger, Melissa A.
Mahoney, Lane J.
Kang, Peter B.
Zanoteli, Edmar
Vissing, John
Witting, Nanna
Echaniz-Laguna, Andoni
Wallgren-Pettersson, Carina
Dowling, James
Merlini, Luciano
Oldfors, Anders
Ousager, Lilian Bomme
Melki, Judith
Krause, Amanda
Jern, Christina
Oliveira, Acary S. B.
Petit, Florence
Jacquette, Aurelia
Chaussenot, Annabelle
Mowat, David
Leheup, Bruno
Cristofano, Michele
Poza Aldea, Juan Jose
Michel, Fabrice
Furby, Alain
Barcena Llona, Jose E.
Van Coster, Rudy
Bertini, Enrico
Urtizberea, Jon Andoni
Drouin-Garraud, Valerie
Beroud, Christophe
Prudhon, Bernard
Bedford, Melanie
Mathews, Katherine
Erby, Lori A. H.
Smith, Stephen A.
Roggenbuck, Jennifer
Crowe, Carol A.
Spitale, Allison Brennan
Johal, Sheila C.
Amato, Anthony A.
Demmer, Laurie A.
Jonas, Jessica
Darras, Basil T.
Bird, Thomas D.
Laurino, Mercy
Welt, Selman I.
Trotter, Cynthia
Guicheney, Pascale
Das, Soma
Mandel, Jean-Louis
Beggs, Alan H.
Laporte, Jocelyn
Institución
Resumen
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. Hum Mutat 33: 949-959, 2012. (C) 2012 Wiley Periodicals, Inc.