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

NCT02380729 | Completed

• 1 other identifier: EA2_107_14
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 3

Brief Summary

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

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

Conditions

Genetic Diseases

Keywords

Health care delivery; Human Phenotype Ontology; Mutation prioritization; Next Generation Sequencing; Mutation detection; Bioinformatic analysis; Quality of life

Outcome Measures

Primary Outcomes (1)

• Diagnostic yield through gene panel sequencing of 3089 known disease genes.

  The number of confirmed disease causing mutations that can be identified in 200 patients following gene panel sequencing and analysis with the PhenIX software.

  6 months.

Secondary Outcomes (3)

• Quality of Life

  2 years

• Manageability of a next generation sequencing (NGS) pipeline in routine clinical diagnostics

  2 years

• Health economy of NGS

  2 years

Study Arms (2)

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; Genetic: Whole Genome Sequencing (WGS)

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)

Interventions

Gene Panel Sequencing GENETIC

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

Index patients

Whole Genome Sequencing (WGS) GENETIC

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.

Index patients; Parents of the index patient

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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
• 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.
• Age: from birth up until age 18 years
• Gender: Both sexes will be included

You may not qualify if:

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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• German Federal Ministry of Education and Research: collaborator

Study Sites (3)

Department of General Pediatrics, Charité-Universitätsmedizin

Berlin, 13353, Germany

Location

Department of Neuropediatrics, Charité-Universitätsmedizin

Berlin, 13353, Germany

Location

Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin

Berlin, 13353, Germany

Location

Related Publications (1)

• Zemojtel T, Kohler S, Mackenroth L, Jager M, Hecht J, Krawitz P, Graul-Neumann L, Doelken S, Ehmke N, Spielmann M, Oien NC, Schweiger MR, Kruger U, Frommer G, Fischer B, Kornak U, Flottmann R, Ardeshirdavani A, Moreau Y, Lewis SE, Haendel M, Smedley D, Horn D, Mundlos S, Robinson PN. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome. Sci Transl Med. 2014 Sep 3;6(252):252ra123. doi: 10.1126/scitranslmed.3009262.

  PMID: 25186178 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

DNA extracted from peripheral blood cells of the index patient and of his/her parents.

MeSH Terms

Conditions

Genetic Diseases, Inborn

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: March 5, 2015
• Study Start: January 31, 2015
• Primary Completion: June 30, 2017
• Study Completion: December 31, 2017
• Last Updated: January 26, 2018

Record last verified: 2018-01

Locations

DE (3)