Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

study id #: NCT02532244

condition: 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

status: Recruiting

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.

intervention: sample collection

results: https://clinicaltrials.gov/ct2/show/results/NCT02532244

last updated: March 03, 2022

start date: June 2015

estimated completion: December 2022

last updated: March 12, 2021

size / enrollment: 300

study 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.

primary outcomes:

• 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 outcomes:

• SMN1 copy number
  up to 2 years
• SMN2 copy number
  up to 2 years
• target gene mRNA levels
  up to 2 years
• target gene protein levels
  up to 2 years

inclusion criteria:

exclusion criteria: Criteria:

not seen by one of the study investigators

sponsor: Nemours Children's Clinic

contacts: Matthew ER Butchbach, Ph.D., 302-298-7366, Matthew.Butchbach@nemours.org

investigators: Matthew ER Butchbach, Ph.D.,Nemours Children's Clinic

trial center locations: United States

• Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
  Matthew ER Butchbach, Ph.D., 302-298-7366, Matthew.Butchbach@nemours.org