Implementation of Molecular Diagnostic Pathways

NCT03084224 | Unknown

• 1 other identifier: CGM-01
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

For some neurological and neurodegenerative diseases genetic inheritance is well documented (described as Mendelian or multifactorial), but sometimes specific mutations or family segregation evidences have not been identified. Considering this scenario, most of the times it is impossible or unlikely to identify the responsible gene, or the private mutation, of a patient affected by a neurodegenerative disease. New technologies such as Next Generation Sequencing (NGS), allow the analysis of hundreds of genes in a single experiment. The implementation of these technologies will help to identify new genes and new variants associated with neurological diseases. Using this approach, several molecular genetic diagnosis will definitely find the needle in a haystack, and will be able to be used in the clinical practice.

Conditions

Genetic Disease

Outcome Measures

Primary Outcomes (1)

• Neurology consulting

  Clinical valuation

  10 days

Secondary Outcomes (2)

• Genetic Counseling

  1 day

• Molecular testing I and/or II level

  3-6 months

Interventions

neurological and neurodegenerative diseases GENETIC

NGS on a large scale of Patients with complexes phenotypes

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients without genetic diagnosis

You may qualify if:

• Clinical criteria for neurogenetic disease

You may not qualify if:

• absence of clinical condition

Sponsors & Collaborators

• Neuromed IRCCS: lead

Study Sites (1)

Stefano Gambardella

Pozzilli, Isernia, 86077, Italy

RECRUITING

Related Publications (10)

• Zhi D, Chen R. Statistical guidance for experimental design and data analysis of mutation detection in rare monogenic mendelian diseases by exome sequencing. PLoS One. 2012;7(2):e31358. doi: 10.1371/journal.pone.0031358. Epub 2012 Feb 10.

  PMID: 22348076 RESULT

• Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008 Apr 17;452(7189):872-6. doi: 10.1038/nature06884.

  PMID: 18421352 RESULT

• Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem. 2009 Apr;55(4):641-58. doi: 10.1373/clinchem.2008.112789. Epub 2009 Feb 26.

  PMID: 19246620 RESULT

• Tucker T, Marra M, Friedman JM. Massively parallel sequencing: the next big thing in genetic medicine. Am J Hum Genet. 2009 Aug;85(2):142-54. doi: 10.1016/j.ajhg.2009.06.022.

  PMID: 19679224 RESULT

• Teer JK, Mullikin JC. Exome sequencing: the sweet spot before whole genomes. Hum Mol Genet. 2010 Oct 15;19(R2):R145-51. doi: 10.1093/hmg/ddq333. Epub 2010 Aug 12.

  PMID: 20705737 RESULT

• Singleton AB. Exome sequencing: a transformative technology. Lancet Neurol. 2011 Oct;10(10):942-6. doi: 10.1016/S1474-4422(11)70196-X.

  PMID: 21939903 RESULT

• Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010 Jan;42(1):30-5. doi: 10.1038/ng.499. Epub 2009 Nov 13.

  PMID: 19915526 RESULT

• Mamanova L, Coffey AJ, Scott CE, Kozarewa I, Turner EH, Kumar A, Howard E, Shendure J, Turner DJ. Target-enrichment strategies for next-generation sequencing. Nat Methods. 2010 Feb;7(2):111-8. doi: 10.1038/nmeth.1419.

  PMID: 20111037 RESULT

• Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 2008 Nov;18(11):1851-8. doi: 10.1101/gr.078212.108. Epub 2008 Aug 19.

  PMID: 18714091 RESULT

• Ferese R, Campopiano R, Scala S, D'Alessio C, Storto M, Buttari F, Centonze D, Logroscino G, Zecca C, Zampatti S, Fornai F, Cianci V, Manfroi E, Giardina E, Magnani M, Suppa A, Novelli G, Gambardella S. Cohort Analysis of 67 Charcot-Marie-Tooth Italian Patients: Identification of New Mutations and Broadening of Phenotype Expression Produced by Rare Variants. Front Genet. 2021 Jul 19;12:682050. doi: 10.3389/fgene.2021.682050. eCollection 2021.

  PMID: 34354735 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples with Parkinson's Disease

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Stefano Gambardella, PhD

  IRCCS Neuromed INM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefano Gambardella, PhD

CONTACT

0039-0865-02660; stefano.gambardela@neuromed.it

Passarelli

CONTACT

0039-0865-915209; direzionescientifica@neuromed.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Target Duration: 8 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Biologist, PhD

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 20, 2017
• Study Start: December 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2025
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)