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

• ClinicalTrials.gov Identifier: NCT02885090
• Recruitment Status: Completed
• First Posted: August 31, 2016
• Last Update Posted: August 31, 2016
• Sponsor: Central Hospital, Nancy, France
• Information provided by (Responsible Party): Central Hospital, Nancy, France

Tracking Information

• First Submitted Date: August 23, 2016
• First Posted Date: August 31, 2016
• Last Update Posted Date: August 31, 2016
• Study Start Date: February 2010
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2016)

Analysis of chromosomal imbalances through comparative genomic hybridization on DNA microarrays [ Time Frame: up to 12 months ]

Search for pathogenic chromosomal imbalance

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Rett Syndrome

Intervention

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.

Study Arms

• Experimental: RTT patient
  Blood sampling
  Intervention: Procedure: Blood sampling
• Experimental: Parents
  Blood sampling. To distinguish between inherited polymorphic variants and potentially deleterious new imbalances.
  Intervention: Procedure: Blood sampling

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2016): 17
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: May 2011
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02885090
• Other Study ID Numbers: 2009-A01147-50
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Central Hospital, Nancy, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Central Hospital, Nancy, France
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christophe PHILIPPE,; Laboratoire de Génétique Médicale, Rue du Morvan, 54511 Vandoeuvre-Les-Nancy Cédex

• PRS Account: Central Hospital, Nancy, France
• Verification Date: August 2016