LTBP4 genotype predicts age of ambulatory loss in duchenne muscular dystrophy

被引：175

作者：

Flanigan, Kevin M. ^{[1
,2
,3
]}

Ceco, Ermelinda ^{[4
]}

Lamar, Kay-Marie ^{[4
]}

Kaminoh, Yuuki ^{[1
]}

Dunn, Diane M. ^{[5
]}

Mendell, Jerry R. ^{[1
,2
,3
]}

King, Wendy M. ^{[3
]}

Pestronk, Alan ^{[6
]}

Florence, Julaine M. ^{[6
]}

Mathews, Katherine D. ^{[7
]}

Finkel, Richard S. ^{[8
,9
]}

Swoboda, Kathryn J. ^{[10
]}

Gappmaier, Eduard ^{[11
]}

Howard, Michael T. ^{[5
]}

Day, John W. ^{[12
]}

McDonald, Craig ^{[13
]}

McNally, Elizabeth M. ^{[4
]}

Weiss, Robert B. ^{[5
]}

机构：

[1] Nationwide Childrens Hosp, Ctr Gene Therapy, Columbus, OH 43205 USA

[2] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA

[4] Univ Chicago, Dept Med, Dept Human Genet, Comm Cell Physiol, Chicago, IL 60637 USA

[5] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA

[6] Washington Univ, Dept Neurol, St Louis, MO USA

[7] Univ Iowa Carver Coll Med, Dept Pediat & Neurol, Iowa City, IA USA

[8] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA

[9] Univ Penn, Pearlman Sch Med, Dept Neurol & Pediat, Philadelphia, PA 19104 USA

[10] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA

[11] Univ Utah, Dept Phys Therapy, Salt Lake City, UT USA

[12] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA

[13] Univ Calif Davis, Dept Phys Med & Rehabil, Sacramento, CA USA

来源：

ANNALS OF NEUROLOGY | 2013年 / 73卷 / 04期

关键词：

GROWTH-FACTOR-BETA; TGF-BETA; CORTICOSTEROID TREATMENT; BINDING; POLYMORPHISMS; ASSOCIATION; ACTIVATION; EXPRESSION;

D O I：

10.1002/ana.23819

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary DMD mutations. Ltbp4, encoding latent transforming growth factor- binding protein 4, was previously discovered in a genome-wide scan as a modifier of murine muscular dystrophy. We sought to determine whether LTBP4 genotype influenced DMD severity in a large patient cohort. Methods We analyzed nonsynonymous single nucleotide polymorphisms (SNPs) from human LTBP4 in 254 nonambulatory subjects with known DMD mutations. These SNPs, V194I, T787A, T820A, and T1140M, form the VTTT and IAAM LTBP4 haplotypes. Results Individuals homozygous for the IAAM LTBP4 haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype. Glucocorticoid-treated patients who were IAAM homozygotes lost ambulation at 12.5 +/- 3.3 years compared to 10.7 +/- 2.1 years for treated VTTT heterozygotes or homozygotes. IAAM fibroblasts exposed to transforming growth factor (TGF) displayed reduced phospho-SMAD signaling compared to VTTT fibroblasts, consistent with LTBP4' role as a regulator of TGF. Interpretation LTBP4 haplotype influences age at loss of ambulation, and should be considered in the management of DMD patients. ANN NEUROL 2013;73:481-488

引用

页码：481 / 488

页数：8

共 27 条

[1] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[2] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[3] EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN DYSTROPHIC PATIENT MUSCLES CORRELATES WITH FIBROSIS - PATHOGENETIC ROLE OF A FIBROGENIC CYTOKINE [J].

BERNASCONI, P ;

TORCHIANA, E ;

CONFALONIERI, P ;

BRUGNONI, R ;

BARRESI, R ;

MORA, M ;

CORNELIO, F ;

MORANDI, L ;

MANTEGAZZA, R .

JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :1137-1144

[4] Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management [J].

Bushby, Katharine ;

Finkel, Richard ;

Birnkrant, David J. ;

Case, Laura E. ;

Clemens, Paula R. ;

Cripe, Linda ;

Kaul, Ajay ;

Kinnett, Kathi ;

McDonald, Craig ;

Pandya, Shree ;

Poysky, James ;

Shapiro, Frederic ;

Tomezsko, Jean ;

Constantin, Carolyn .

LANCET NEUROLOGY, 2010, 9 (01) :77-93

[5] Early onset of inflammation and later involvement of TGFβ in Duchenne muscular dystrophy [J].

Chen, YW ;

Nagaraju, K ;

Bakay, M ;

McIntyre, O ;

Rawat, R ;

Shi, R ;

Hoffman, EP .

NEUROLOGY, 2005, 65 (06) :826-834

[6] Angiotensin II type 1 receptor blockade attenuates TGF-β-induced failure of muscle regeneration in multiple myopathic states [J].

Cohn, Ronald D. ;

van Erp, Christel ;

Habashi, Jennifer P. ;

Soleimani, Arshia A. ;

Klein, Erin C. ;

Lisi, Matthew T. ;

Gamradt, Matthew ;

Rhys, Colette M. ap ;

Holm, Tammy M. ;

Loeys, Bart L. ;

Ramirez, Francesco ;

Judge, Daniel P. ;

Ward, Christopher W. ;

Dietz, Harry C. .

NATURE MEDICINE, 2007, 13 (02) :204-210

[7] Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort [J].

Dent, KM ;

Dunn, DM ;

von Niederhausern, AC ;

Aoyagi, AT ;

Kerr, L ;

Bromberg, MB ;

Hart, KJ ;

Tuohy, T ;

White, S ;

den Dunnen, JT ;

Weiss, RB ;

Flanigan, KM .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2005, 134A (03) :295-298

[8] Nonsense Mutation-Associated Becker Muscular Dystrophy: Interplay Between Exon Definition and Splicing Regulatory Elements within the DMD Gene [J].

Flanigan, Kevin M. ;

Dunn, Diane M. ;

von Niederhausern, Andrew ;

Soltanzadeh, Payam ;

Howard, Michael T. ;

Sampson, Jacinda B. ;

Swoboda, Kathryn J. ;

Bromberg, Mark B. ;

Mendell, Jerry R. ;

Taylor, Laura E. ;

Anderson, Christine B. ;

Pestronk, Alan ;

Florence, Julaine M. ;

Connolly, Anne M. ;

Mathews, Katherine D. ;

Wong, Brenda ;

Finkel, Richard S. ;

Bonnemann, Carsten G. ;

Day, John W. ;

McDonald, Craig ;

Weiss, Robert B. .

HUMAN MUTATION, 2011, 32 (03) :299-308

[9] Mutational Spectrum of DMD Mutations in Dystrophinopathy Patients: Application of Modern Diagnostic Techniques to a Large Cohort [J].

Flanigan, Kevin M. ;

Dunn, Diane M. ;

von Niederhausern, Andrew ;

Soltanzadeh, Payam ;

Gappmaier, Eduard ;

Howard, Michael T. ;

Sampson, Jacinda B. ;

Mendell, Jerry R. ;

Wall, Cheryl ;

King, Wendy M. ;

Pestronk, Alan ;

Florence, Julaine M. ;

Connolly, Anne M. ;

Mathews, Katherine D. ;

Stephan, Carrie M. ;

Laubenthal, Karla S. ;

Wong, Brenda L. ;

Morehart, Paula J. ;

Meyer, Amy ;

Finkel, Richard S. ;

Bonnemann, Carsten G. ;

Medne, Livija ;

Day, John W. ;

Dalton, Joline C. ;

Margolis, Marcia K. ;

Hinton, Veronica J. ;

Weiss, Robert B. .

HUMAN MUTATION, 2009, 30 (12) :1657-1666

[10] Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression [J].

Foersti, Asta ;

Li, Xuchen ;

Wagner, Kerstin ;

Tavelin, Bjorn ;

Enquist, Kerstin ;

Palmqvist, Richard ;

Altieri, Andrea ;

Hallmans, Goran ;

Hemminki, Kari ;

Lenner, Per .

GENES CHROMOSOMES & CANCER, 2010, 49 (03) :270-281

← 1 2 3 →