Molecular and Genetic Studies of Congenital Myopathies

NCT00272883 | Recruiting

• 3 other identifiers: 03-08-128RAR44345NS40828
• Study Type: observational
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

In the Congenital Myopathy Research Program at Boston Children's Hospital and Harvard Medical School, the researchers are studying the congenital myopathies (neuromuscular diseases present from birth), including central core disease, centronuclear/myotubular myopathy, congenital fiber type disproportion, multiminicore disease, nemaline myopathy, rigid spine muscular dystrophy, SELENON (SEPN1), RYR1 myopathy, ADSS1 (ADSSL) Myopathy and undefined congenital myopathies. The primary goal of the research is to better understand the genes and proteins (gene products) involved in muscle functioning and disease. The researchers hope that our studies will allow for improved diagnosis and treatment of individuals with congenital myopathies in the future. For more information, visit the Laboratory Website at www.childrenshospital.org/research/beggs

Conditions

Central Core Disease; Centronuclear Myopathy; Congenital Fiber Type Disproportion; Multiminicore Disease; Myotubular Myopathy; Nemaline Myopathy; Rigid Spine Muscular Dystrophy; Undefined Congenital Myopathy

Keywords

central core; centronuclear; multiminicore; multicore; minicore; congenital fiber type disproportion; myotubular; nemaline; congenital myopathy; neuromuscular; rigid spine

Outcome Measures

Primary Outcomes (1)

• Identification of Neuromuscular Disease Genes

  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 Outcomes (1)

• Characterization of Clinical Features of Congenital Myopathies

  The time frame for disease classification and genotype-phenotype correlation is unpredictable and may range from several days to several decades.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a clinical or suspected diagnosis of a congenital myopathy and their family members.

You may qualify if:

• Individuals with a clinical or suspected diagnosis of a congenital myopathy and their family members

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Muscular Dystrophy Association: collaborator

Study Sites (1)

Genetics Division, Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (18)

• 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.

  PMID: 16042307 RESULT

• 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.

  PMID: 15236405 RESULT

• 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.

  PMID: 12601110 RESULT

• 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.

  PMID: 11558787 RESULT

• 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.

  PMID: 15056467 RESULT

• 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.

  PMID: 12677001 RESULT

• 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.

  PMID: 12196661 RESULT

• 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.

  PMID: 10508519 RESULT

• 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.

  PMID: 10192379 RESULT

• 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.

  PMID: 10051637 RESULT

• 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.

  PMID: 21357678 RESULT

• 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.

  PMID: 19953533 RESULT

• 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.

  PMID: 19944167 RESULT

• 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.

  PMID: 19562689 RESULT

• 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.

  PMID: 19346529 RESULT

• 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.

  PMID: 19232495 RESULT

• 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.

  PMID: 17537630 RESULT

• 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.

  PMID: 17160903 RESULT

Related Links

• The Beggs lab website

Biospecimen

Retention: SAMPLES WITH DNA

The primary biospecimens retained are blood, saliva and muscle tissue samples. Other specimens are retained on a case-by-case basis.

MeSH Terms

Conditions

Myopathy, Central Core; Myopathies, Structural, Congenital; Minicore Myopathy with External Ophthalmoplegia; Myopathies, Nemaline; Myotonia Congenita

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Alan H. Beggs, Ph.D.

  Children's Hospital Boston/Harvard Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Casie Genetti, M.S. C.G.C.

CONTACT

(617) 919-2169; BeggsLabGC@childrens.harvard.edu

Beggs lab

CONTACT

beggslab@enders.tch.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sir Edwin & Lady Manton Professor of Pediatrics

Study Record Dates

• First Submitted: January 5, 2006
• First Posted: January 9, 2006
• Study Start: August 1, 2003
• Primary Completion (Estimated): January 1, 2050
• Study Completion (Estimated): January 1, 2050
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

US (1)