Clinical Trial: Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

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.

Detailed Summary:

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.


Sponsor: Nemours Children's Clinic

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Nemours Children's Clinic

Dates:
Date Received: August 21, 2015
Date Started: June 2015
Date Completion: December 2022
Last Updated: August 24, 2015
Last Verified: August 2015