Clinical trial NCT02885090: New Genes Involved in Molecular Etiology of Rett Syndrome Through DNA Microarray Comparative Genomic Hybridization
Official title: Search for New Genes Involved in Molecular Etiology of Rett Syndrome Through Comparative Genomic Hybridization on DNA Microarrays
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rett Syndrome
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-08-31
Enrollment: 17
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Rett syndrome (RTT) is a genetic encephalopathy and the typical form is caused by mutations in the gene MECP2. It is a genetically heterogeneous pathology. CDKL5 and FOXG1 have been recently discovered being involved in other forms of RTT. However, at least 5% of typical forms and more other atypical forms are not linked to any of 3 genes known to be involved in the disease.

The purpose of this study is to identify new genes involved in molecular etiology of typical and atypical forms of RTT.

Detailed description: Search for pathogenic chromosomal imbalance through comparative genomic hybridization (aCGH) on DNA microarrays will be done in a group of patients having typical or atypical forms of RTT without known mutations in MECP2, CDKL5 et FOXG1B genes.

After imbalance confirmation by qPCR, the pathogenic potential of the segmental aneusomy will be assigned according to the interpretation of aCGH technique-dedicated DECEPHER, BACH and GVD databases. Analysis of parents will allow distinguishing between inherited polymorphic variants and potentially deleterious new imbalances.

In case of a new imbalance, a bioinformatics approach will look for candidate genes that will be possibly confirmed by classic mutation screening (sequencing and PCR) in all typical and atypical cases of RTT present in the cohort.

The identification of new genes involved in RTT will ameliorate the molecular diagnosis of the disease and genetic counseling for families. This project will allow progression in comprehension of physiopathological mechanisms of cerebral development abnormalities

Eligibility criteria: Inclusion Criteria:

* Patients: RETT syndrome
* Patients: Female
* Parents: parent of a patients

Primary outcomes:
measure: Analysis of chromosomal imbalances through comparative genomic hybridization on DNA microarrays
timeFrame: up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Besançon
country: France
facility: Handicaps de l'Enfant - Pavillon Ste Marie, CHU St Jacques
city: Besançon
country: France
facility: Service de Neuropédiatrie, Hôpital St Jacques, CHU de Besançon
city: Caen
country: France
facility: Unité de génétique, Groupe hospitalier Hôpital Flaubert
city: Dijon
country: France
facility: Centre de Génétique Hôpital d'Enfants, CHU de Dijon
city: Montpellier
country: France
facility: Service de neuropédiatrie, CHU Hôpital Gui de Chauliac
city: Nice
country: France
facility: Laboratoire de Génétique chromosomique, CHU Hôpital l'Archet 2
city: Nice
country: France
facility: Service de génétique médicale, CHU Hôpital Purpan
city: Toulouse
country: France
facility: Service de génétique médicale, CHU Hôpital Purpan, CHU de Toulouse
city: Vandoeuvre les Nancy
country: France
facility: Laboratoire de Génétique, Hôpitaux de Brabois, CHU de Nancy
Study officials:
affiliation: Laboratoire de Génétique Médicale, Rue du Morvan, 54511 Vandoeuvre-Les-Nancy Cédex
name: Christophe PHILIPPE,
role: PRINCIPAL_INVESTIGATOR
References: