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Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02532244
Recruitment Status : Recruiting
First Posted : August 25, 2015
Last Update Posted : February 21, 2020
Information provided by (Responsible Party):
Matthew E. R. Butchbach, Ph.D., Nemours Children's Clinic

Brief Summary:
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a motor neuron or a neuromuscular disorder and their family members. The samples to be collected will be obtained using either non-invasive (saliva and buccal swabs) or minimally invasive (whole blood) means. The research team will then extract high quality genomic DNA from these samples and use it to identify and confirm novel gene mutations and to identify genes which regulate the severity of motor neuron/neuromuscular diseases.

Condition or disease Intervention/treatment
Spinal Muscular Atrophy Charcot-Marie-Tooth Disease Muscular Dystrophy Spinal Muscular Atrophy With Respiratory Distress 1 Amyotrophic Lateral Sclerosis Motor Neuron Disease Neuromuscular Disease Peroneal Muscular Atrophy Fragile X Syndrome Other: sample collection

Detailed Description:

Diseases affecting the motor unit--which is composed of the motor neuron, its myelin sheath and its innervated muscle fibers--are a diverse, heterogeneous group having heterogeneous clinical presentations and genetic causes. Many of these disorders have a inherited component. In some cases, the genetics underlying a given neuromuscular/motor neuron disease, like spinal muscular atrophy (SMA) or Duchenne muscular dystrophy, are well characterized. There are, however, disorders whose genetic basis has yet to be determined or genetically characterized diseases which harbor novel mutations. The purpose of this genetic registry is to catalogue early-onset motor neuron and neuromuscular disorders and to determine their genetic bases. With samples obtained from this registry, the investigators will be able to provide a genetic diagnosis for a specific neuromuscular/motor neuron disease which will lead to better care for those patients affected by these diseases.

Many of these disorders have a wide spectrum of phenotypic variability. For example, the severity of SMA is quite variable even though it is caused by the loss of a single gene, i.e. survival motor neuron 1 (SMN1). The number of copies of the duplicated gene survival motor neuron 2 (SMN2) dictates phenotypic severity in SMA. In this study, the research team will also identify potential modifiers of phenotypic severity for specific disorders like SMA and Charcot-Marie-Tooth (CMT) disease. With the identification of novel modifier genes, the investigators will be able to more accurately predict disease outcomes and the investigators will also have novel targets for the development of therapeutic agents for these diseases.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
Actual Study Start Date : June 2015
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Group/Cohort Intervention/treatment
sample collection
Each participant will have blood drawn for genetic analysis and for establishment of a lymphoblastoid cell line. The investigator will also collect saliva and buccal swabs for genetic analysis
Other: sample collection
collection of blood, saliva and buccal cells

Primary Outcome Measures :
  1. genetic diagnosis [ Time Frame: up to 2 years ]
    The genetic basis for the subject's condition will be verified/determined by Sanger sequencing of DNA sample

Secondary Outcome Measures :
  1. SMN1 copy number [ Time Frame: up to 2 years ]
    The number of copies of the SMN1 gene will be determined using array digital polymerase chain reaction (PCR).

  2. SMN2 copy number [ Time Frame: up to 2 years ]
    The number of copies of the SMN2 gene will be determined using array digital PCR.

  3. target gene mRNA levels [ Time Frame: up to 2 years ]
    The relative levels of the disease gene-specific messenger ribonucleic acid (mRNA) will be measured using quantitative PCR.

  4. target gene protein levels [ Time Frame: up to 2 years ]
    The relative amounts of the disease-gene-specific protein will be measured using immunoblot.

Biospecimen Retention:   Samples With DNA
serum, lymphoblastoid cell lines derived from peripheral blood mononuclear cells, saliva, buccal cells

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
This study will enroll children diagnosed with a motor neuron or neuromuscular disease as well as their parents and/or siblings.

Inclusion Criteria:

  • Diagnosis of motor neuron/neuromuscular disease confirmed by neurologist
  • Be seen by one of the study investigators

Exclusion Criteria:

  • not seen by one of the study investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02532244

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Contact: Matthew ER Butchbach, Ph.D. 302-298-7366
Contact: Kimberly Klipner, M.S. 302-651-4088

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United States, Delaware
Alfred I. duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Matthew ER Butchbach, Ph.D.    302-298-7366   
Sub-Investigator: Mena Scavina, D.O.         
Sub-Investigator: William Mackenzie, M.D.         
Sub-Investigator: Robert Heinle, M.D.         
Sponsors and Collaborators
Nemours Children's Clinic
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Principal Investigator: Matthew ER Butchbach, Ph.D. Nemours Children's Clinic
Publications of Results:
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Responsible Party: Matthew E. R. Butchbach, Ph.D., Research Scientist, Nemours Children's Clinic Identifier: NCT02532244    
Other Study ID Numbers: 764456
First Posted: August 25, 2015    Key Record Dates
Last Update Posted: February 21, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified information will be shared once the data are published.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Matthew E. R. Butchbach, Ph.D., Nemours Children's Clinic:
distal hereditary motor neuronopathy
Additional relevant MeSH terms:
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Muscular Dystrophies
Tooth Diseases
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Muscular Atrophy
Muscular Atrophy, Spinal
Neuromuscular Diseases
Fragile X Syndrome
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Pathological Conditions, Anatomical
Neurodegenerative Diseases
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Neuromuscular Manifestations
Neurologic Manifestations
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Sex Chromosome Disorders