Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

Study Overview
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Brief Summary
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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 minimally invasive (whole blood) means. The research team will then extract high quality genomic DNA or RNA 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.

Detailed Description
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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.

Official Title
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Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

Conditions
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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

Intervention / Treatment
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* Other: sample collection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sample collection<br>Each participant will have blood drawn for genetic analysis and for establishment of a lymphoblastoid cell line. | Other: sample collection<br>* collection of blood<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| genetic diagnosis | The genetic basis for the subject's condition will be verified/determined by Sanger sequencing of DNA sample | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SMN1 copy number | The number of copies of the SMN1 gene will be determined using array digital polymerase chain reaction (PCR). | up to 2 years | 
| SMN2 copy number | The number of copies of the SMN2 gene will be determined using array digital PCR. | up to 2 years | 
| target gene mRNA levels | The relative levels of the disease gene-specific messenger ribonucleic acid (mRNA) will be measured using quantitative PCR. | up to 2 years | 
| target gene protein levels | The relative amounts of the disease-gene-specific protein will be measured using immunoblot. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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distal hereditary motor neuronopathy