New Genes Involved in Molecular Etiology of Rett Syndrome Through DNA Microarray Comparative Genomic Hybridization

Not Applicable

Completed

• Conditions: Rett Syndrome
• Interventions: Procedure: Blood sampling

• Registration Number: NCT02885090
• Lead Sponsor: Central Hospital, Nancy, France

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

Study Timeline

• Study Start: 2010-02
• Primary Completion: 2011-05
• Study Completion: 2011-05
• Status Verified: 2016-08
• Study First Submitted: 2016-08-23
• Study First Submitted QC: 2016-08-26
• Last Update Submitted: 2016-08-26
• Study First Posted: 2016-08-31
• Last Update Posted: 2016-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Parents	Blood sampling	Blood sampling. To distinguish between inherited polymorphic variants and potentially deleterious new imbalances.
RTT patient	Blood sampling	Blood sampling

Primary Outcome Measures

Name	Time	Method
Analysis of chromosomal imbalances through comparative genomic hybridization on DNA microarrays	up to 12 months	Search for pathogenic chromosomal imbalance

Trial Locations

Locations (9)

Handicaps de l'Enfant - Pavillon Ste Marie, CHU St Jacques; 🇫🇷 Besançon, France

Service de Neuropédiatrie, Hôpital St Jacques, CHU de Besançon; 🇫🇷 Besançon, France

Unité de génétique, Groupe hospitalier Hôpital Flaubert; 🇫🇷 Caen, France

Centre de Génétique Hôpital d'Enfants, CHU de Dijon; 🇫🇷 Dijon, France

Service de neuropédiatrie, CHU Hôpital Gui de Chauliac; 🇫🇷 Montpellier, France

Laboratoire de Génétique chromosomique, CHU Hôpital l'Archet 2; 🇫🇷 Nice, France

Service de génétique médicale, CHU Hôpital Purpan; 🇫🇷 Nice, France

Service de génétique médicale, CHU Hôpital Purpan, CHU de Toulouse; 🇫🇷 Toulouse, France

Laboratoire de Génétique, Hôpitaux de Brabois, CHU de Nancy; 🇫🇷 Vandoeuvre les Nancy, France