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

Search for New Genes Involved in Molecular Etiology of Rett Syndrome Through Comparative Genomic Hybridization on DNA Microarrays

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.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Procedure: Blood sampling

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • Handicaps de l'Enfant - Pavillon Ste Marie, CHU St Jacques
  • Besançon, France
    • Service de Neuropédiatrie, Hôpital St Jacques, CHU de Besançon
  • Caen, France
    • Unité de génétique, Groupe hospitalier Hôpital Flaubert
  • Dijon, France
    • Centre de Génétique Hôpital d'Enfants, CHU de Dijon
  • Montpellier, France
    • Service de neuropédiatrie, CHU Hôpital Gui de Chauliac
  • Nice, France
    • Laboratoire de Génétique chromosomique, CHU Hôpital l'Archet 2
  • Nice, France
    • Service de génétique médicale, CHU Hôpital Purpan
  • Toulouse, France
    • Service de génétique médicale, CHU Hôpital Purpan, CHU de Toulouse
  • Vandoeuvre les Nancy, France
    • Laboratoire de Génétique, Hôpitaux de Brabois, CHU de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RTT patient; Blood sampling	Procedure: Blood sampling; In children: 2 EDTA tubes of 7 ml, 1 Heparin Li tube of 5 ml and 2 PAXgene tubes of 2.5 ml (max 0.8-0.9 ml blood/kg) In parents: 2 EDTA tubes of 7 ml, 1 Heparin Li tube of 5 ml.
EXPERIMENTAL: Parents; Blood sampling. To distinguish between inherited polymorphic variants and potentially deleterious new imbalances.	Procedure: Blood sampling; In children: 2 EDTA tubes of 7 ml, 1 Heparin Li tube of 5 ml and 2 PAXgene tubes of 2.5 ml (max 0.8-0.9 ml blood/kg) In parents: 2 EDTA tubes of 7 ml, 1 Heparin Li tube of 5 ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of chromosomal imbalances through comparative genomic hybridization on DNA microarrays	Search for pathogenic chromosomal imbalance	up to 12 months

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Christophe PHILIPPE,, Laboratoire de Génétique Médicale, Rue du Morvan, 54511 Vandoeuvre-Les-Nancy Cédex

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: August 23, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (ESTIMATE): August 31, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): August 31, 2016
• Last Update Submitted That Met QC Criteria: August 26, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: 2009-A01147-50

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO