Molecular Analysis of Patients With Neuromuscular Disease

Molecular Analysis of Nucleic Acids Derived From Patients With Neuromuscular Disease and Their Family Members

The purpose of this study is to identify new genes responsible for neuromuscular disorders and study muscle tissue of patient with known 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 with no causative gene implicated in their disease. Using molecular genetics to unravel basis of these neuromuscular disorders will lead to more accurate diagnosis/prognosis of these disorders which will lead to potential therapies.

Study Overview

• Status: Recruiting
• Conditions: Limb-girdle Muscular Dystrophy; Neuromuscular; Disorder, Hereditary; Duchenne/Becker Muscular Dystrophy

Detailed Description

We are looking to discover new disease genes 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; DMD gene, 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 biopsy samples in patients with known and unknown types of neuromuscular disease has led to new insights into disease pathophysiology, which we hope will aid in finding new treatments.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Casie Genetti, MS,LCGC; Phone Number: 617-919-2169; Email: Casie.Genetti@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Casie Genetti, MS, LCGC; Phone Number: 617-919-2169; Email: Casie.Genetti@childrens.harvard.edu
      • Principal Investigator: Louis M Kunkel, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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 and their family members.

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 a neuromuscular diagnosis in you or a family member
2. not wishing to participate
3. being incapable of giving consent and not having a legal guardian willing or able to do so

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Louis M Kunkel, PhD, Boston Children's Hospital/Harvard Medical School

Publications and helpful links

General Publications

• 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 alpha 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.
• Saha M, Reddy HM, Salih MA, Estrella E, Jones MD, Mitsuhashi S, Cho KA, Suzuki-Hatano S, Rizzo SA, Hamad MH, Mukhtar MM, Hamed AA, Elseed MA, Lek M, Valkanas E, MacArthur DG, Kunkel LM, Pacak CA, Draper I, Kang PB. Impact of PYROXD1 deficiency on cellular respiration and correlations with genetic analyses of limb-girdle muscular dystrophy in Saudi Arabia and Sudan. Physiol Genomics. 2018 Nov 1;50(11):929-939. doi: 10.1152/physiolgenomics.00036.2018. Epub 2018 Aug 31.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2002
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: October 17, 2006
• First Submitted That Met QC Criteria: October 17, 2006
• First Posted (Estimate): October 19, 2006

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Neuromuscular Disease; Muscle atrophy; Muscle weakness
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Dystrophies, Limb-Girdle; Neuromuscular Diseases
• Other Study ID Numbers: 03-12-205; 5R01NS080929 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be de-identified to protect privacy, but maybe shared with other researchers.
• IPD Sharing Time Frame: Once a participant is enrolled, we will keep the data indefinitely.
• IPD Sharing Access Criteria: Data will only be shared with collaborating scientists once a patient enrolls. Data will be shared according to choice on individual consent forms.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No