NCT02380729

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 200 (actual)
• Sponsor: Charite University, Berlin, Germany · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Genetic Diseases

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2015-01-31
• Primary completion: 2017-06-30
• Completion: 2017-12-31
• First posted: 2015-03-05
• Last updated: 2018-01-26

Locations

3 sites across 1 country: Germany