Genodermatosis, Rare Genetic Disease With Cutaneous Expression
Conditions
Keywords
Genodermatosis, genetic, children
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.
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.)
Interventions
GENETICGenetic diagnostic by mendeliome or genome
For cases not explained by a mendeliomes: genome and transcriptome on fibroblast culture
Sponsors
Center of Human Genetics - ULB in Brussels
Interuniversity Institute of Bioinformatics in Brussels
Queen Fabiola Children's University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genetic diagnostic by mendeliome | 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
| Measure | Time frame | Description |
|---|---|---|
| Genetic diagnostic by genome | 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. |
| Genetic diagnostic by fibroblast transcriptome | 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. |
| Relevance of dermatological symptoms | 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 |
Countries
Belgium
Contacts
Primary ContactDeborah Salik, MD
Backup ContactGuillaume Smits, MD PhD
Outcome results
None listed