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

Johann Böhm; Valérie Biancalana; Elizabeth T Dechene; Marc Bitoun; Christopher R Pierson; Elise Schaefer; Hatice Karasoy; Melissa A Dempsey; Fabrice Klein; Nicolas Dondaine; Christine Kretz; Nicolas Haumesser; Claire Poirson; Anne Toussaint; Rebecca S Greenleaf; Melissa A Barger; Lane J Mahoney; Peter B Kang; Edmar Zanoteli; John Vissing; Nanna Witting; Andoni Echaniz-Laguna; Carina Wallgren-Pettersson; James Dowling; Luciano Merlini; Anders Oldfors; Lilian Bomme Ousager; Judith Melki; Amanda Krause; Christina Jern; Acary S B Oliveira; Florence Petit; Aurélia Jacquette; Annabelle Chaussenot; David Mowat; Bruno Leheup; Michele Cristofano; Juan José Poza Aldea; Fabrice Michel; Alain Furby; Jose E Barcena Llona; Rudy Van Coster; Enrico Bertini; Jon Andoni Urtizberea; Valérie Drouin-Garraud; Christophe Béroud; Bernard Prudhon; Melanie Bedford; Katherine Mathews; Lori A H Erby; Stephen A Smith; Jennifer Roggenbuck; Carol A Crowe; Allison Brennan Spitale; Sheila C Johal; Anthony A Amato; Laurie A Demmer; Jessica Jonas; Basil T Darras; Thomas D Bird; Mercy Laurino; Selman I Welt; Cynthia Trotter; Pascale Guicheney; Soma Das; Jean-Louis Mandel; Alan H Beggs; Jocelyn Laporte

doi:10.1002/humu.22067

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

Johann Böhm, Valérie Biancalana, Elizabeth T Dechene, Marc Bitoun, Christopher R Pierson, Elise Schaefer, Hatice Karasoy, Melissa A Dempsey, Fabrice Klein, Nicolas Dondaine, Christine Kretz, Nicolas Haumesser, Claire Poirson, Anne Toussaint, Rebecca S Greenleaf, Melissa A Barger, Lane J Mahoney, Peter B Kang, Edmar Zanoteli, John VissingNanna Witting, Andoni Echaniz-Laguna, Carina Wallgren-Pettersson, James Dowling, Luciano Merlini, Anders Oldfors, Lilian Bomme Ousager, Judith Melki, Amanda Krause, Christina Jern, Acary S B Oliveira, Florence Petit, Aurélia Jacquette, Annabelle Chaussenot, David Mowat, Bruno Leheup, Michele Cristofano, Juan José Poza Aldea, Fabrice Michel, Alain Furby, Jose E Barcena Llona, Rudy Van Coster, Enrico Bertini, Jon Andoni Urtizberea, Valérie Drouin-Garraud, Christophe Béroud, Bernard Prudhon, Melanie Bedford, Katherine Mathews, Lori A H Erby, Stephen A Smith, Jennifer Roggenbuck, Carol A Crowe, Allison Brennan Spitale, Sheila C Johal, Anthony A Amato, Laurie A Demmer, Jessica Jonas, Basil T Darras, Thomas D Bird, Mercy Laurino, Selman I Welt, Cynthia Trotter, Pascale Guicheney, Soma Das, Jean-Louis Mandel, Alan H Beggs, Jocelyn Laporte

79 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Human Mutation
Vol/bind	33
Udgave nummer	6
Sider (fra-til)	949-59
Antal sider	11
ISSN	1059-7794
DOI	https://doi.org/10.1002/humu.22067
Status	Udgivet - jun. 2012

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10.1002/humu.22067

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Böhm, J., Biancalana, V., Dechene, E. T., Bitoun, M., Pierson, C. R., Schaefer, E., Karasoy, H., Dempsey, M. A., Klein, F., Dondaine, N., Kretz, C., Haumesser, N., Poirson, C., Toussaint, A., Greenleaf, R. S., Barger, M. A., Mahoney, L. J., Kang, P. B., Zanoteli, E., ... Laporte, J. (2012). Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. Human Mutation, 33(6), 949-59. https://doi.org/10.1002/humu.22067

Böhm, J, Biancalana, V, Dechene, ET, Bitoun, M, Pierson, CR, Schaefer, E, Karasoy, H, Dempsey, MA, Klein, F, Dondaine, N, Kretz, C, Haumesser, N, Poirson, C, Toussaint, A, Greenleaf, RS, Barger, MA, Mahoney, LJ, Kang, PB, Zanoteli, E, Vissing, J, Witting, N, Echaniz-Laguna, A, Wallgren-Pettersson, C, Dowling, J, Merlini, L, Oldfors, A, Bomme Ousager, L, Melki, J, Krause, A, Jern, C, Oliveira, ASB, Petit, F, Jacquette, A, Chaussenot, A, Mowat, D, Leheup, B, Cristofano, M, Poza Aldea, JJ, Michel, F, Furby, A, Llona, JEB, Van Coster, R, Bertini, E, Urtizberea, JA, Drouin-Garraud, V, Béroud, C, Prudhon, B, Bedford, M, Mathews, K, Erby, LAH, Smith, SA, Roggenbuck, J, Crowe, CA, Brennan Spitale, A, Johal, SC, Amato, AA, Demmer, LA, Jonas, J, Darras, BT, Bird, TD, Laurino, M, Welt, SI, Trotter, C, Guicheney, P, Das, S, Mandel, J-L, Beggs, AH & Laporte, J 2012, 'Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy', Human Mutation, bind 33, nr. 6, s. 949-59. https://doi.org/10.1002/humu.22067

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

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.",

author = "Johann B{\"o}hm and Val{\'e}rie Biancalana and Dechene, {Elizabeth T} and Marc Bitoun and Pierson, {Christopher R} and Elise Schaefer and Hatice Karasoy and Dempsey, {Melissa A} and Fabrice Klein and Nicolas Dondaine and Christine Kretz and Nicolas Haumesser and Claire Poirson and Anne Toussaint and Greenleaf, {Rebecca S} and Barger, {Melissa A} and Mahoney, {Lane J} and Kang, {Peter B} and Edmar Zanoteli and John Vissing and Nanna Witting and Andoni Echaniz-Laguna and Carina Wallgren-Pettersson and James Dowling and Luciano Merlini and Anders Oldfors and {Bomme Ousager}, Lilian and Judith Melki and Amanda Krause and Christina Jern and Oliveira, {Acary S B} and Florence Petit and Aur{\'e}lia Jacquette and Annabelle Chaussenot and David Mowat and Bruno Leheup and Michele Cristofano and {Poza Aldea}, {Juan Jos{\'e}} and Fabrice Michel and Alain Furby and Llona, {Jose E Barcena} and {Van Coster}, Rudy and Enrico Bertini and Urtizberea, {Jon Andoni} and Val{\'e}rie Drouin-Garraud and Christophe B{\'e}roud and Bernard Prudhon and Melanie Bedford and Katherine Mathews and Erby, {Lori A H} and Smith, {Stephen A} and Jennifer Roggenbuck and Crowe, {Carol A} and {Brennan Spitale}, Allison and Johal, {Sheila C} and Amato, {Anthony A} and Demmer, {Laurie A} and Jessica Jonas and Darras, {Basil T} and Bird, {Thomas D} and Mercy Laurino and Welt, {Selman I} and Cynthia Trotter and Pascale Guicheney and Soma Das and Jean-Louis Mandel and Beggs, {Alan H} and Jocelyn Laporte",

note = "{\textcopyright} 2012 Wiley Periodicals, Inc.",

year = "2012",

month = jun,

doi = "10.1002/humu.22067",

language = "English",

volume = "33",

pages = "949--59",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "JohnWiley & Sons, Inc.",

number = "6",

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TY - JOUR

T1 - Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

AU - Böhm, Johann

AU - Biancalana, Valérie

AU - Dechene, Elizabeth T

AU - Bitoun, Marc

AU - Pierson, Christopher R

AU - Schaefer, Elise

AU - Karasoy, Hatice

AU - Dempsey, Melissa A

AU - Klein, Fabrice

AU - Dondaine, Nicolas

AU - Kretz, Christine

AU - Haumesser, Nicolas

AU - Poirson, Claire

AU - Toussaint, Anne

AU - Greenleaf, Rebecca S

AU - Barger, Melissa A

AU - Mahoney, Lane J

AU - Kang, Peter B

AU - Zanoteli, Edmar

AU - Vissing, John

AU - Witting, Nanna

AU - Echaniz-Laguna, Andoni

AU - Wallgren-Pettersson, Carina

AU - Dowling, James

AU - Merlini, Luciano

AU - Oldfors, Anders

AU - Bomme Ousager, Lilian

AU - Melki, Judith

AU - Krause, Amanda

AU - Jern, Christina

AU - Oliveira, Acary S B

AU - Petit, Florence

AU - Jacquette, Aurélia

AU - Chaussenot, Annabelle

AU - Mowat, David

AU - Leheup, Bruno

AU - Cristofano, Michele

AU - Poza Aldea, Juan José

AU - Michel, Fabrice

AU - Furby, Alain

AU - Llona, Jose E Barcena

AU - Van Coster, Rudy

AU - Bertini, Enrico

AU - Urtizberea, Jon Andoni

AU - Drouin-Garraud, Valérie

AU - Béroud, Christophe

AU - Prudhon, Bernard

AU - Bedford, Melanie

AU - Mathews, Katherine

AU - Erby, Lori A H

AU - Smith, Stephen A

AU - Roggenbuck, Jennifer

AU - Crowe, Carol A

AU - Brennan Spitale, Allison

AU - Johal, Sheila C

AU - Amato, Anthony A

AU - Demmer, Laurie A

AU - Jonas, Jessica

AU - Darras, Basil T

AU - Bird, Thomas D

AU - Laurino, Mercy

AU - Welt, Selman I

AU - Trotter, Cynthia

AU - Guicheney, Pascale

AU - Das, Soma

AU - Mandel, Jean-Louis

AU - Beggs, Alan H

AU - Laporte, Jocelyn

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

U2 - 10.1002/humu.22067

DO - 10.1002/humu.22067

M3 - Journal article

C2 - 22396310

SN - 1059-7794

VL - 33

SP - 949

EP - 959

JO - Human Mutation

JF - Human Mutation

IS - 6

ER -

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

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