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Trial record 5 of 9029 for:    Genetic Diseases, Inborn AND genetic disorder

Mutation Exploration in Non-acquired, Genetic Disorders and Its Impact on Health Economy and Life Quality (MENDEL)

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ClinicalTrials.gov Identifier: NCT02380729
Recruitment Status : Completed
First Posted : March 5, 2015
Last Update Posted : January 26, 2018
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Markus Schuelke, M.D., Charite University, Berlin, Germany

Brief Summary:

The MENDEL-study will investigate whether the use of gene panel or whole genome sequencing (WGS) will:

  1. improve the rate of diagnosis and through this compare the performance of the two diagnostic approaches (gene panel vs. WGS),
  2. investigate whether use of said sequencing approaches early in the diagnostic process results in reduced health care spending, and
  3. result in an improved quality of life for the patients and their parents.

Condition or disease Intervention/treatment
Genetic Diseases Genetic: Gene Panel Sequencing Genetic: Whole Genome Sequencing (WGS)

Detailed Description:

Patients will be recruited from in- and outpatient clinics at the Otto Heubner Center, the Berlin Center for Rare Diseases, and the Institute for Medical Genetics and Human Genetics at Charité-Universitätsmedizin Berlin, Germany. Following informed consent, 5 ml EDTA blood will be obtained from the index case and 10 ml blood from each parent. Disease related phenotype information and the outcome of previous diagnostic tests and procedures will be recorded as part of Study visit #1.

[1] Study visit #1

  1. A medical genetics physical will be performed. Detailed clinical symptoms (phenotype) will be recorded using Human Phenotype Ontology (HPO) terminology.
  2. A detailed pedigree will be drawn.
  3. Age of disease onset will be determined.
  4. Results from previous diagnostic tests and procedures, as well as hospital stays, will be recorded.
  5. The parents will be asked to complete a validated, standardized quality of life questionnaire adapted for for rare disease. The questionnaire is available online or in paper form.

[2] Study visit #2a (optional)

This study visit will only take place in the event that gene panel sequencing identifies a variant of uncertain significance, where additional information would be needed in order to determine its pathogenicity (e.g. confirmational biochemical testing, collection of additional information). Relevant research findings will be discussed and the nature and necessity of the additional testing will be explained.

[3] Study visit #2b (optional)

This study visit will only take place in the event that WGS identifies a variant of uncertain significance where additional information is needed in order to determine its pathogenicity > see Study visit #2a.

[4] Study visit #3 (results session)

Results will be returned in the context of a genetic counseling session.

[5] Study visit #4 (6 months after Study visit #3)

The parents will be asked to complete the validated, standardized quality of life questionnaire adapted for rare disease again.


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Study Type : Observational
Actual Enrollment : 200 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Mutation Exploration in Non-acquired, Genetic Disorders and Its Impact on Health Economy and Life Quality
Actual Study Start Date : January 31, 2015
Actual Primary Completion Date : June 30, 2017
Actual Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Index patients

Children between birth and 18 years of age manifesting with a suspected genetic disorder.

Investigation: First Gene Panel Sequencing and if no mutation ist found > Whole Genome Sequencing (WGS)

Genetic: Gene Panel Sequencing
Enrichment for and panel sequencing of 2942 disease genes listed in the Online Mendelian Inheritance of Man (OMIM) database.

Genetic: Whole Genome Sequencing (WGS)
Whole Genome Sequencing of the index case and of both parents in the event that Gene Panel Sequencing did not identify a disease-causing mutation.

Parents of the index patient

Both parents of the index patient.

Investigation: Whole Genome Sequencing (WGS) if no mutation is found by Gene Panel Sequencing of the index patient.

Genetic: Whole Genome Sequencing (WGS)
Whole Genome Sequencing of the index case and of both parents in the event that Gene Panel Sequencing did not identify a disease-causing mutation.




Primary Outcome Measures :
  1. Diagnostic yield through gene panel sequencing of 3089 known disease genes. [ Time Frame: 6 months. ]
    The number of confirmed disease causing mutations that can be identified in 200 patients following gene panel sequencing and analysis with the PhenIX software.


Secondary Outcome Measures :
  1. Quality of Life [ Time Frame: 2 years ]
    Assessment of the parents' quality of life before and after molecular diagnostics and reception of a molecular genetic diagnosis.

  2. Manageability of a next generation sequencing (NGS) pipeline in routine clinical diagnostics [ Time Frame: 2 years ]
    Calculation of the duration [months] between recruitment of a family and the final genetic counselling.

  3. Health economy of NGS [ Time Frame: 2 years ]
    Comparison of the cost of "standard diagnostics" versus the use of gene panel sequencing or WGS at an early stage in the diagnostic process. Health economic analysis of the costs incurred for each patient through "the standard diagnostic approach" in comparison to costs incurred through the use of gene panel sequencing/WGS.


Biospecimen Retention:   Samples With DNA
DNA extracted from peripheral blood cells of the index patient and of his/her parents.


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Index patients: Children (age newborn to 18 years) who present with a suspected genetic disorder

Parents: biological mother and father of each index case.

Criteria

Inclusion Criteria:

  1. Diagnosis: Suspicion of genetic disease. (Only one of the following criteria is required.) [1.1] Family member(s) with similar phenotype OR [1.2] At least two affected organ systems OR [1.3] One affected organ system that is known to be associated with multiple disease causing genes (e.g. long QT syndrome) OR [1.4] Multiple birth defects
  2. Both parents must be available for blood draw in order to confirm phase (segregation analysis) or in order to perform WGS of the trio at a later time point.
  3. Age: from birth up until age 18 years
  4. Gender: Both sexes will be included

Exclusion Criteria:

  1. Suspicion that the phenotype is due to an acquired disease
  2. Missing informed consent from both parents or from all legal guardians for genetic testing in the setting of a clinical trial.
  3. Clinical diagnosis of a disease with a known monogenic cause, e.g. Phenylketonuria or Cystic fibrosis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02380729


Locations
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Germany
Department of General Pediatrics, Charité-Universitätsmedizin
Berlin, Germany, 13353
Department of Neuropediatrics, Charité-Universitätsmedizin
Berlin, Germany, 13353
Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin
Berlin, Germany, 13353
Sponsors and Collaborators
Charite University, Berlin, Germany
German Federal Ministry of Education and Research
Investigators
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Principal Investigator: Markus Schuelke, M.D. Department of Neuropediatrics, Charité
Principal Investigator: Stefan Mundlos, M.D. Institute of Medical Genetics and of Human Genetics, Charité
Principal Investigator: Heiko Krude, M.D. Department of General Pediatrics, Charité

Additional Information:
Publications:
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Responsible Party: Markus Schuelke, M.D., Professor, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT02380729     History of Changes
Other Study ID Numbers: EA2_107_14
First Posted: March 5, 2015    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: January 2018
Keywords provided by Markus Schuelke, M.D., Charite University, Berlin, Germany:
Health care delivery
Human Phenotype Ontology
Mutation prioritization
Next Generation Sequencing
Mutation detection
Bioinformatic analysis
Quality of life
Additional relevant MeSH terms:
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Genetic Diseases, Inborn