Method of Genetic Analysis in Genodermatoses (GENODERM)

Development of a Genetic Analysis Method by Mendeliomes and Genomes in the Diagnosis of Genodermatoses and Rare Genetic Diseases With Cutaneous Expression

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.

Study Overview

• Status: Unknown
• Conditions: Genodermatosis; Rare Genetic Disease With Cutaneous Expression
• Intervention / Treatment: Genetic: Genetic diagnostic by mendeliome or genome

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.)

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Deborah Salik, MD; Phone Number: 0032 2 477 31 20; Email: Deborah.salik@huderf.be
• Study Contact Backup: Name: Guillaume Smits, MD PhD; Email: Guillaume.smits@erasme.ulb.ac.be

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Recruiting
    • Hôpital Universitaire Des Enfants Rein Fabiola
    • Contact: Deborah Salik, MD; Phone Number: 0032 2 477 31 20; Email: Deborah.salik@huderf.be
    • Principal Investigator: Deborah Salik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic diagnostic by mendeliome	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.	At time of clinical diagnosis of genodermatosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic diagnostic by genome	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.	At time of clinical diagnosis of genodermatosis
Genetic diagnostic by fibroblast transcriptome	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.	At time of clinical diagnosis of genodermatosis
Relevance of dermatological symptoms	Correlation between dermatological signs and symptoms and a genetic diagnosis established by the mendelioma, genome and transcriptome method	At time of clinical diagnosis of genodermatosis

Collaborators and Investigators

• Sponsor: Queen Fabiola Children's University Hospital
• Collaborators: Center of Human Genetics - ULB in Brussels; Interuniversity Institute of Bioinformatics in Brussels
• Investigators: Principal Investigator: Deborah Salik, MD, Hôpital Universitaire Des Enfants Rein Fabiola

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: children; genetic; Genodermatosis
• Additional Relevant MeSH Terms: Skin Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic
• Other Study ID Numbers: P2018/Dermato/Genodermatose

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No