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Method of Genetic Analysis in Genodermatoses (GENODERM)

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ClinicalTrials.gov Identifier: NCT03873285
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : April 15, 2019
Sponsor:
Collaborators:
Center of Human Genetics - ULB in Brussels
Interuniversity Institute of Bioinformatics in Brussels
Information provided by (Responsible Party):
Queen Fabiola Children's University Hospital

Brief Summary:
The goal of the study is to develop a method of genetic diagnosis in two stages, by mendelioma then by genome and transcriptome on fibroblast culture, in genodermatoses and rare diseases with cutaneous expression in the child.

Condition or disease Intervention/treatment Phase
Genodermatosis Rare Genetic Disease With Cutaneous Expression Genetic: Genetic diagnostic by mendeliome or genome Not Applicable

Detailed Description:

Interventional multicenter prospective study. Patients will be examined by a dermatologist to describe and identify the various skin lesions Collaboration with the geneticist team: clinical examination for relevant cases Patient records will be consulted. Relevant medical information, biological examinations and other complementary examinations will be studied.

A blood sample (10 ml in EDTA tube) will be collected from the patient and his/her parents to store DNA for mediome and genome.

A written parental and child consent (if age-appropriate) will be obtained and a study information sheet will be signed. They will also sign the usual genetic consent request for mendeliome, genome and transcriptome on culture of fibroblasts.

A 4 mm punch skin biopsy (healthy or damaged depending on phenotype and indication) will be performed according to the standard technique.

The fibroblast culture will be performed routinely by the Genetics Center Transcriptome will be done according to the processes set up at the Genetics Center Mendeliome analysis

  • Allow the analysis of 4000 rare disease genes
  • Will be performed according to routine analyzes of the genetics lab
  • Uses the Highlander tools (web)
  • Use of de novo filters, autosomal recessive, heterozygous compound, X linked, strong variant (LOF and canonical splice sites)
  • Use of rarer filters: exomic or gene deletion, splicing (+/- 12 base pairs around exons)
  • In unexplained severe cases, a genome supplemented with the 10Xgenomics method and a transcriptome of fibroblasts will be realized. This double strategy afford to get a genome of high interpretative quality. Genome analysis by the 10Xgenomics method (https://www.10xgenomics.com )
  • This method allows us to deconvolate haplotypes and allows the analysis of 16,000 other complementary genes and to obtain precisely defined structural variants.
  • The transcriptome will better assess the genomic effects on gene expression.
  • The genome and transcriptome will also assess the presence of deep intron mutations and their effect on splicing, and will be a sustainable resource for other long-term projects (analysis of non-coding regions, microRNAs, etc.)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Development of a Genetic Analysis Method by Mendeliomes and Genomes in the Diagnosis of Genodermatoses and Rare Genetic Diseases With Cutaneous Expression
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Arm Intervention/treatment
Experimental: Genodermatosis patients
Children between 0 to 18 years old with the presence of dermatological symptoms suggesting genodermatosis or presence of systemic symptoms in an undiagnosed patient associated with dermatological manifestations suggestive of a more rare genetic disorder with cutaneous expression
Genetic: Genetic diagnostic by mendeliome or genome
For cases not explained by a mendeliomes: genome and transcriptome on fibroblast culture




Primary Outcome Measures :
  1. Genetic diagnostic by mendeliome [ Time Frame: At time of clinical diagnosis of genodermatosis ]
    Proportion of patients for whom a genetic diagnosis has been established using the mendeliome method. American College of Medical Genetics and Genomics. Diagnostic variants are classified as "pathogenic" or "probably pathogenic" variants.


Secondary Outcome Measures :
  1. Genetic diagnostic by genome [ Time Frame: At time of clinical diagnosis of genodermatosis ]
    Proportion of patients for whom a genetic diagnosis has been established using the genome method. American College of Medical Genetics and Genomics. Diagnostic variants are classified as "pathogenic" or "probably pathogenic" variants.

  2. Genetic diagnostic by fibroblast transcriptome [ Time Frame: At time of clinical diagnosis of genodermatosis ]
    Proportion of patients for whom a genetic diagnosis has been established using the fibroblast transcriptome method. American College of Medical Genetics and Genomics. Diagnostic variants are classified as "pathogenic" or "probably pathogenic" variants.

  3. Relevance of dermatological symptoms [ Time Frame: At time of clinical diagnosis of genodermatosis ]
    Correlation between dermatological signs and symptoms and a genetic diagnosis established by the mendelioma, genome and transcriptome method



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children between 0 to 18 years old
  • Presence of dermatological symptoms suggesting genodermatosis
  • Presence of systemic symptoms in an undiagnosed patient associated with dermatological manifestations suggestive of a more rare genetic disorder with cutaneous expression

Exclusion Criteria:

  • Mosaicism
  • Neurofibromatosis, all type
  • Tuberous sclerosis
  • Ichthyosis vulgaris
  • Suspicion of somatic impairment (giant nevus)

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): NCT03873285


Contacts
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Contact: Deborah Salik, MD 0032 2 477 31 20 Deborah.salik@huderf.be
Contact: Guillaume Smits, MD PhD Guillaume.smits@erasme.ulb.ac.be

Locations
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Belgium
Hôpital Universitaire Des Enfants Rein Fabiola Recruiting
Brussels, Belgium, 1020
Contact: Deborah Salik, MD    0032 2 477 31 20    Deborah.salik@huderf.be   
Principal Investigator: Deborah Salik, MD         
Sponsors and Collaborators
Queen Fabiola Children's University Hospital
Center of Human Genetics - ULB in Brussels
Interuniversity Institute of Bioinformatics in Brussels
Investigators
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Principal Investigator: Deborah Salik, MD Hôpital Universitaire Des Enfants Rein Fabiola

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Responsible Party: Queen Fabiola Children's University Hospital
ClinicalTrials.gov Identifier: NCT03873285     History of Changes
Other Study ID Numbers: P2018/Dermato/Genodermatose
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: April 15, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Queen Fabiola Children's University Hospital:
Genodermatosis
genetic
children

Additional relevant MeSH terms:
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Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases