Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

NCT02532244 | Completed

• 1 other identifier: 764456
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 3

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 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.

Conditions

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

distal hereditary motor neuronopathy

Outcome Measures

Primary Outcomes (1)

• 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 (4)

• 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

Study Arms (1)

sample collection

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

Other: sample collection

Interventions

sample collection OTHER

collection of blood

sample collection

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll children diagnosed with a motor neuron or neuromuscular disease as well as their parents and/or siblings as well as adults with childhood-onset motor neuron or neuromuscular diseases.

You may qualify if:

• Diagnosis of motor neuron/neuromuscular disease confirmed by neurologist
• Be seen by one of the study investigators

You may not qualify if:

• not seen by one of the study investigators

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (3)

Nemours Children's Hospital Delaware

Wilmington, Delaware, 19803, United States

Location

Nemours Children's Specialty Care

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Hospital Orlando

Orlando, Florida, 32827, United States

Location

Related Publications (6)

• 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.

  PMID: 28284873 RESULT

• 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.

  PMID: 26247043 RESULT

• 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.

  PMID: 32066871 RESULT

• 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.

  PMID: 33199817 RESULT

• 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.

  PMID: 33415588 RESULT

• 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.

  PMID: 35741345 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

serum, lymphoblastoid cell lines derived from peripheral blood mononuclear cells, saliva, buccal cells

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Charcot-Marie-Tooth Disease; Muscular Dystrophies; Spinal muscular atrophy with respiratory distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Polyneuropathies; Peripheral Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Matthew ER Butchbach, Ph.D.

  Nemours Children's Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: August 25, 2015
• Study Start: June 1, 2015
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: December 19, 2024

Record last verified: 2024-12

Locations

US (3)