Molecular Analysis of Patients With Neuromuscular Disease

Study Description

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Brief Summary:

The purpose of this study is to identify genes and proteins responsible for nerve and muscle disorders by studying genetic material from individuals with neuromuscular disease, as well as their family members. We are interested in recruiting many types of neuromuscular disease including; Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and limb-girdle muscle dystrophy (LGMD). There are still many patients diagnosed with muscular dystrophy but have no causative gene implicated in their disease. We feel that these patients may have new genetic changes in genes coding for important muscle proteins that we have yet to identify. Using molecular genetics to unravel the biochemical basis of these neuromuscular disorders should lead to more accurate diagnosis of these disorders and should lead to potential therapies.

Condition or disease
Limb-girdle Muscular Dystrophy; Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Facioscapulohumeral Muscular Dystrophy

Detailed Description:

We aim to identify and characterize the genetic changes responsible for the neuromuscular diseases found in our participants and their families. Our research lab has a long history of identifying novel genes responsible for various forms of neuromuscular disease including; dystrophin, the sarcoglycans, obscurin, and filamin. Each discovery has resulted in advances in our ability to develop diagnostic tests which benefit patients and their families by providing accurate diagnosis, presymptomatic and/or prenatal testing. Genotype-phenotype correlation studies have increased our understanding of the natural history of these rare disorders benefiting patients through better prognostic determinations by clinicians. Biochemical and pathological analysis of muscle biopsies in patient with known and unknown types of neuromuscular disease has led to new insights into disease pathophysiology which we hope will aid in finding treatments.

Study Design

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Study Type :	Observational
Estimated Enrollment :	1000 participants
Observational Model:	Family-Based
Time Perspective:	Prospective
Official Title:	Molecular Analysis of Nucleic Acids Derived From Patients With Neuromuscular Disease and Their Family Members
Actual Study Start Date :	January 2002
Estimated Primary Completion Date :	December 31, 2020
Estimated Study Completion Date :	December 31, 2021

Groups and Cohorts

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Outcome Measures

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Biospecimen Retention:   Samples With DNA

DNA from blood or saliva and muscle samples from proband DNA from blood or saliva from family members Skin biopsy from proband and family members

Eligibility Criteria

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Ages Eligible for Study:	up to 100 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Families will be ascertained world-wide as the muscular dystrophies are a pan-ethinic group of diseases.

Criteria

The samples used in this study will be derived from individuals at risk for, or suffering from, neuromuscular disease, generally resulting in clinical weakness of one or more muscle groups.

Inclusion criteria:

1. having a clinical and/or pathological diagnosis of a muscular dystrophy
2. being the first degree relative of someone with such a diagnosis
3. having had a muscle biopsy if diagnosed with a neuromuscular disease
4. willingness to provide a skin biopsy for research only

Exclusion Criteria:

1. not having such a diagnosis and not being related to such an individual
2. not wishing to participate
3. being incapable of giving consent and not having a legal guardian willing or able to do so

Contacts and Locations

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Contacts

Contact: Elicia A Estrella, MS, LCGC	617-919-4552	elicia.estrella@childrens.harvard.edu
Contact: Casie Genetti, MS,LCGC	617-919-2169	Casie.Genetti@childrens.harvard.edu

Locations

United States, Massachusetts
Children's Hospital Boston	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Elicia A Estrella, MS, LCGC 617-919-4552 elicia.estrella@childrens.harvard.edu
Contact: Casie Genetti, MS, LCGC 617-919-2169 Casie.Genetti@childrens.harvard.edu
Principal Investigator: Louis M Kunkel, PhD

Sponsors and Collaborators

Boston Children’s Hospital

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Louis M Kunkel, PhD	Children's Hospital Boston/Harvard Medical School

More Information

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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Kunkel lab website 

Study Data/Documents: Kunkel lab newsletters 

Publications of Results:

Vieira NM, Spinazzola JM, Alexander MS, Moreira YB, Kawahara G, Gibbs DE, Mead LC, Verjovski-Almeida S, Zatz M, Kunkel LM. Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):6080-6085. doi: 10.1073/pnas.1703556114. Epub 2017 May 22.

Reddy HM, Cho KA, Lek M, Estrella E, Valkanas E, Jones MD, Mitsuhashi S, Darras BT, Amato AA, Lidov HG, Brownstein CA, Margulies DM, Yu TW, Salih MA, Kunkel LM, MacArthur DG, Kang PB. The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States. J Hum Genet. 2017 Feb;62(2):243-252. doi: 10.1038/jhg.2016.116. Epub 2016 Oct 6.

Other Publications:

Vieira NM, Elvers I, Alexander MS, Moreira YB, Eran A, Gomes JP, Marshall JL, Karlsson EK, Verjovski-Almeida S, Lindblad-Toh K, Kunkel LM, Zatz M. Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype. Cell. 2015 Nov 19;163(5):1204-1213. doi: 10.1016/j.cell.2015.10.049. Epub 2015 Nov 12.

Responsible Party:	Louis Kunkel, Professor of Genetics and Pediatrics, Harvard Medical School, Boston Children’s Hospital
ClinicalTrials.gov Identifier:	NCT00390104 History of Changes
Other Study ID Numbers:	03-12-205; 5R01NS080929 ( U.S. NIH Grant/Contract )
First Posted:	October 19, 2006
Last Update Posted:	July 11, 2017
Last Verified:	July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Individual participant data maybe shared with other researchers, but participant samples will be de-identified.

Keywords provided by Louis Kunkel, Boston Children’s Hospital:

Neuromuscular Disease; Muscle weakness; Muscle atrophy

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Neuromuscular Diseases; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Facioscapulohumeral; Muscular Disorders, Atrophic	Muscular Diseases; Musculoskeletal Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked