- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00272883
Molecular and Genetic Studies of Congenital Myopathies
Molecular Analysis of Neuromuscular Disease
Study Overview
Status
Detailed Description
The Congenital Myopathy Research Program consists of a group of scientists and healthcare providers all working to better understand the congenital myopathies. We are taking two approaches to reach our research goals. The first involves identifying and describing new genes and proteins involved in the skeletal muscles that allow our bodies to move. Simultaneously, studies are underway to identify genetic changes (mutations) that cause human neuromuscular disease. Thus, our second approach is to identify mutations, learn how they are inherited in families, and understand how they lead to weakness in individuals with neuromuscular disease. These approaches allow correlation of our basic muscle biology findings with our studies on muscle tissue of affected individuals.
Our research would not be possible without the generous participation of individuals and families with congenital myopathies. Participation in our studies is free of charge. Travel to Boston is not required, and we welcome the participation of individuals from around the world.
We appreciate the participation of all individuals with a congenital myopathy, as well as their first-degree relatives. Participants with a congenital myopathy are asked to donate medical records, a blood or saliva sample, and a muscle tissue sample (if available). Participating relatives are asked to donate a blood sample. The blood/saliva sample is used to acquire DNA (genetic material) which can be used to identify genetic changes and to study how a disease is inherited in a family. The medical records are employed to understand a participant's symptoms. The muscle tissue is used to better understand the disease at the muscular level by studying the gene expression and protein levels in individuals with congenital myopathies.
For more information, visit the Laboratory Website at www.childrenshospital.org/research/beggs.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Casie Genetti, M.S. C.G.C.
- Phone Number: (617) 919-2169
- Email: BeggsLabGC@childrens.harvard.edu
Study Contact Backup
- Name: Beggs lab
- Email: beggslab@enders.tch.harvard.edu
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Recruiting
- Genetics Division, Boston Children's Hospital
-
Contact:
- Casie Genetti, M.S. C.G.C.
- Phone Number: 617-919-2169
- Email: BeggsLabGC@childrens.harvard.edu
-
Principal Investigator:
- Alan H. Beggs, Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Individuals with a clinical or suspected diagnosis of a congenital myopathy and their family members
Exclusion Criteria:
- No specific exclusion criteria. Our studies do not include myotonia congenita or related conditions.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Other
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identification of Neuromuscular Disease Genes
Time Frame: The time frame for disease gene discovery is unpredictable and may range from several days to several decades.
|
This is an ongoing genetic discovery study aimed at finding and confirming pathogenic mutations in known and new disease genes.
|
The time frame for disease gene discovery is unpredictable and may range from several days to several decades.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Characterization of Clinical Features of Congenital Myopathies
Time Frame: The time frame for disease classification and genotype-phenotype correlation is unpredictable and may range from several days to several decades.
|
As known as known and new disease genes are identified the resulting genotypes are correlated with subject phenotypes.
|
The time frame for disease classification and genotype-phenotype correlation is unpredictable and may range from several days to several decades.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Alan H. Beggs, Ph.D., Children's Hospital Boston/Harvard Medical School
Publications and helpful links
General Publications
- Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol. 2005 Jul;64(7):555-64. doi: 10.1097/01.jnen.0000171653.17213.2e.
- Agrawal PB, Strickland CD, Midgett C, Morales A, Newburger DE, Poulos MA, Tomczak KK, Ryan MM, Iannaccone ST, Crawford TO, Laing NG, Beggs AH. Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations. Ann Neurol. 2004 Jul;56(1):86-96. doi: 10.1002/ana.20157.
- Ryan MM, Ilkovski B, Strickland CD, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield LK, De Girolami U, Iannaccone ST, Laing NG, North KN, Beggs AH. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology. 2003 Feb 25;60(4):665-73. doi: 10.1212/01.wnl.0000046585.81304.bc.
- Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN. Nemaline myopathy: a clinical study of 143 cases. Ann Neurol. 2001 Sep;50(3):312-20. doi: 10.1002/ana.1080.
- Sanoudou D, Frieden LA, Haslett JN, Kho AT, Greenberg SA, Kohane IS, Kunkel LM, Beggs AH. Molecular classification of nemaline myopathies: "nontyping" specimens exhibit unique patterns of gene expression. Neurobiol Dis. 2004 Apr;15(3):590-600. doi: 10.1016/j.nbd.2003.12.013.
- Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH. Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4666-71. doi: 10.1073/pnas.0330960100. Epub 2003 Apr 3.
- Wattanasirichaigoon D, Swoboda KJ, Takada F, Tong HQ, Lip V, Iannaccone ST, Wallgren-Pettersson C, Laing NG, Beggs AH. Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. Neurology. 2002 Aug 27;59(4):613-7. doi: 10.1212/wnl.59.4.613.
- Nowak KJ, Wattanasirichaigoon D, Goebel HH, Wilce M, Pelin K, Donner K, Jacob RL, Hubner C, Oexle K, Anderson JR, Verity CM, North KN, Iannaccone ST, Muller CR, Nurnberg P, Muntoni F, Sewry C, Hughes I, Sutphen R, Lacson AG, Swoboda KJ, Vigneron J, Wallgren-Pettersson C, Beggs AH, Laing NG. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet. 1999 Oct;23(2):208-12. doi: 10.1038/13837.
- North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH. A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet. 1999 Apr;21(4):353-4. doi: 10.1038/7675. No abstract available.
- Pelin K, Hilpela P, Donner K, Sewry C, Akkari PA, Wilton SD, Wattanasirichaigoon D, Bang ML, Centner T, Hanefeld F, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2305-10. doi: 10.1073/pnas.96.5.2305.
- Ottenheijm CA, Lawlor MW, Stienen GJ, Granzier H, Beggs AH. Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy. Hum Mol Genet. 2011 May 15;20(10):2015-25. doi: 10.1093/hmg/ddr084. Epub 2011 Feb 28.
- Lawlor MW, Dechene ET, Roumm E, Geggel AS, Moghadaszadeh B, Beggs AH. Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion. Hum Mutat. 2010 Feb;31(2):176-83. doi: 10.1002/humu.21157.
- Ottenheijm CA, Hooijman P, DeChene ET, Stienen GJ, Beggs AH, Granzier H. Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2). J Struct Biol. 2010 May;170(2):334-43. doi: 10.1016/j.jsb.2009.11.013. Epub 2009 Nov 26.
- Laing NG, Dye DE, Wallgren-Pettersson C, Richard G, Monnier N, Lillis S, Winder TL, Lochmuller H, Graziano C, Mitrani-Rosenbaum S, Twomey D, Sparrow JC, Beggs AH, Nowak KJ. Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Hum Mutat. 2009 Sep;30(9):1267-77. doi: 10.1002/humu.21059.
- Ottenheijm CA, Witt CC, Stienen GJ, Labeit S, Beggs AH, Granzier H. Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. Hum Mol Genet. 2009 Jul 1;18(13):2359-69. doi: 10.1093/hmg/ddp168. Epub 2009 Apr 4.
- Lehtokari VL, Greenleaf RS, DeChene ET, Kellinsalmi M, Pelin K, Laing NG, Beggs AH, Wallgren-Pettersson C. The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence. Neuromuscul Disord. 2009 Mar;19(3):179-81. doi: 10.1016/j.nmd.2008.12.001. Epub 2009 Feb 15.
- Pierson CR, Agrawal PB, Blasko J, Beggs AH. Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy. Neuromuscul Disord. 2007 Jul;17(7):562-8. doi: 10.1016/j.nmd.2007.03.010. Epub 2007 May 29. Erratum In: Neuromuscul Disord. 2008 Jun;18(6):519.
- Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007 Jan;80(1):162-7. doi: 10.1086/510402. Epub 2006 Nov 14.
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 03-08-128R
- AR44345
- NS40828
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Centronuclear Myopathy
-
Newcastle-upon-Tyne Hospitals NHS TrustRecruitingX-linked Myotubular Myopathy | Centronuclear Myopathy | Myotubular Myopathy | Myotubular Myopathy 1 | Myotubular (Centronuclear) Myopathy | Centronuclear Myopathy, X-LinkedUnited Kingdom
-
Institut de Myologie, FranceDynacureCompletedCentronuclear MyopathyFrance, Belgium, Germany, Italy, Spain
-
Vastra Gotaland RegionEnrolling by invitationMusculoskeletal Diseases | Neuromuscular Diseases | Centronuclear Myopathy | Nemaline Myopathy | Congenital Myopathy | Myosin Storage MyopathySweden
-
DynacureWithdrawnCentronuclear MyopathyGermany, France
-
DynacureTerminatedCentronuclear MyopathyFrance, Netherlands, United Kingdom, Belgium, Denmark, Germany
-
DynacureWithdrawnCentronuclear Myopathy
-
Radboud University Medical CenterUMC UtrechtNot yet recruitingCentronuclear Myopathy | Nemaline Myopathy | Central Core Disease | Multi-Minicore DiseaseNetherlands
-
Ultragenyx Pharmaceutical IncTerminatedHereditary Inclusion Body Myopathy | GNE Myopathy | Inclusion Body Myopathy 2 | Distal Myopathy With Rimmed Vacuoles | Distal Myopathy, Nonaka Type | Quadriceps Sparing MyopathyCanada, United States, Bulgaria
-
James DowlingCanadian Institutes of Health Research (CIHR); Cures Within Reach; The Joshua... and other collaboratorsRecruitingX Linked Myotubular MyopathyUnited Kingdom, Canada, United States
-
Ultragenyx Pharmaceutical IncTerminatedHereditary Inclusion Body Myopathy | GNE Myopathy | Distal Myopathy With Rimmed Vacuoles | Distal Myopathy, Nonaka Type | Quadriceps Sparing MyopathyUnited States, Canada, United Kingdom, Israel, Italy, Bulgaria, France