Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

NCT ID: NCT02532244

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

230 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-06-30

Study Completion Date

2024-12-18

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.

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

Keywords

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distal hereditary motor neuronopathy

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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sample collection

Each participant will have blood drawn for genetic analysis and for establishment of a lymphoblastoid cell line.

sample collection

Intervention Type OTHER

collection of blood

Interventions

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sample collection

collection of blood

Intervention Type OTHER

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
Minimum Eligible Age

1 Month

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Nemours Children's Clinic

OTHER

Sponsor Role lead

Responsible Party

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Matthew E. R. Butchbach, Ph.D.

Research Scientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Matthew ER Butchbach, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Nemours Children's Clinic

Locations

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Nemours Children's Hospital Delaware

Wilmington, Delaware, United States

Site Status

Nemours Children's Specialty Care

Jacksonville, Florida, United States

Site Status

Nemours Children's Hospital Orlando

Orlando, Florida, United States

Site Status

Countries

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United States

References

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Stabley DL, Holbrook J, Harris AW, Swoboda KJ, Crawford TO, Sol-Church K, Butchbach MER. Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR. Neuromuscul Disord. 2017 May;27(5):439-446. doi: 10.1016/j.nmd.2017.02.002. Epub 2017 Feb 6.

Reference Type RESULT
PMID: 28284873 (View on PubMed)

Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME. SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. Mol Genet Genomic Med. 2015 Jul;3(4):248-57. doi: 10.1002/mgg3.141. Epub 2015 Mar 21.

Reference Type RESULT
PMID: 26247043 (View on PubMed)

Chen X, Sanchis-Juan A, French CE, Connell AJ, Delon I, Kingsbury Z, Chawla A, Halpern AL, Taft RJ; NIHR BioResource; Bentley DR, Butchbach MER, Raymond FL, Eberle MA. Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data. Genet Med. 2020 May;22(5):945-953. doi: 10.1038/s41436-020-0754-0. Epub 2020 Feb 18.

Reference Type RESULT
PMID: 32066871 (View on PubMed)

Jiang L, Lin R, Gallagher S, Zayac A, Butchbach MER, Hung P. Development and validation of a 4-color multiplexing spinal muscular atrophy (SMA) genotyping assay on a novel integrated digital PCR instrument. Sci Rep. 2020 Nov 16;10(1):19892. doi: 10.1038/s41598-020-76893-7.

Reference Type RESULT
PMID: 33199817 (View on PubMed)

Stabley DL, Holbrook J, Scavina M, Crawford TO, Swoboda KJ, Robbins KM, Butchbach MER. Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR. Neurogenetics. 2021 Mar;22(1):53-64. doi: 10.1007/s10048-020-00630-5. Epub 2021 Jan 7.

Reference Type RESULT
PMID: 33415588 (View on PubMed)

Pinto A, Cunha C, Chaves R, Butchbach MER, Adega F. Comprehensive In Silico Analysis of Retrotransposon Insertions within the Survival Motor Neuron Genes Involved in Spinal Muscular Atrophy. Biology (Basel). 2022 May 27;11(6):824. doi: 10.3390/biology11060824.

Reference Type RESULT
PMID: 35741345 (View on PubMed)

Other Identifiers

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764456

Identifier Type: -

Identifier Source: org_study_id