Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
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|ClinicalTrials.gov Identifier: NCT02532244|
Recruitment Status : Recruiting
First Posted : August 25, 2015
Last Update Posted : February 21, 2020
|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|
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.
|Study Type :||Observational|
|Estimated Enrollment :||300 participants|
|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|
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
- 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
- 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).
- SMN2 copy number [ Time Frame: up to 2 years ]The number of copies of the SMN2 gene will be determined using array digital PCR.
- 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.
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT02532244
|Contact: Matthew ER Butchbach, Ph.D.||302-298-7366||Matthew.Butchbach@nemours.org|
|Contact: Kimberly Klipner, M.S.||302-651-4088||Kimberly.Klipner@nemours.org|
|United States, Delaware|
|Alfred I. duPont Hospital for Children||Recruiting|
|Wilmington, Delaware, United States, 19803|
|Contact: Matthew ER Butchbach, Ph.D. 302-298-7366 Matthew.Butchbach@nemours.org|
|Sub-Investigator: Mena Scavina, D.O.|
|Sub-Investigator: William Mackenzie, M.D.|
|Sub-Investigator: Robert Heinle, M.D.|
|Principal Investigator:||Matthew ER Butchbach, Ph.D.||Nemours Children's Clinic|