Microarray Analysis in Syndromic Obesity

Not Applicable

Completed

• Conditions: Mental Retardation; Syndromic Obesity

• Registration Number: NCT01043198
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

Comparative genomic hybridization (CGH) array technology has been used in numerous studies on mental retardation, and few chromosomal abnormalities have been identified in patients. Because chromosomal abnormalities have still been associated with obesity, we can expect that syndromic obesity is also associated with small deletions/duplications. Characterization of deleted or duplicated loci in these obese patients would mean that these loci include genes implicated in obesity. This will permit to propose new gene(s) involved in obesity. (In french: Caractérisation phénotypique et recherche de REManiements chromosomiques chez des patients présentant une OBésité syndromique de cause non identifiée : REMOB)

Detailed Description

With the introduction of array comparative genomic hybridization (CGH), genome-wide high resolution analysis for DNA copy number alterations became feasible. This technology has been principally used in patients with mental retardation. Depending on the eligibility criteria and resolution of the array, around 10 % of patients with mental retardation are found with cryptic chromosomal imbalance. This figure arises 20 % for patients with mental retardation and multiple congenital anomalies. Alteration of the lipid metabolism and/or regulation of satiety, obesity (except in presence of other "exogen" factors) can be considered as a developmental disorder. Also, different syndromes with obesity have been associated with chromosomal abnormalities, such as 1p36 deletion syndrome, 2q37 deletion syndrome, chromosome 14 maternal disomy ... So we can expect that syndromic obesity is similarly associated with sub cryptic chromosomal abnormalities. Some "isolated" patients with obesity have been described with cryptic chromosomal imbalance found by array CGH, but no study has been realized in cohorts of patients selected for syndromic obesity.

Characterization of cryptic chromosomal anomaly(ies) in a patient will also be useful to precise the management and follow-up of the patient and to give the family an adapted genetic counselling.

We will define a cohort of patients with syndromic obesity and propose them to realize a first screening looking for the "common" aetiologies of syndromic obesity. If this screening is normal, array CGH will be realized. This analysis implies a blood sampling of 5 ml in patient and his parents.

Genes present at the deleted or duplicated loci characterized in the patients will be study to determine if some could be specifically implicated in the development of obesity. These same genes could be implicated in isolated obesity. Our study will be also useful to precise the aetiological screening of syndromic obesity, and determine the place of array-CGH.

Study Timeline

• Study First Submitted: 2009-12-29
• Study First Submitted QC: 2010-01-05
• Study First Posted: 2010-01-06
• Study Start: 2010-02
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-13
• Last Update Posted: 2012-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• children (under 18 year-old)

• obesity (following IOTF definition)

• at least one criteria among :

  • mental retardation
  • facial dysmorphism
  • at least one major malformation (uro-genital, cardiac, skeletal, cerebral, ophthalmologic...)

Exclusion Criteria

• common obesity
• obesity with an identified aetiology

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Evaluation of the prevalence of cryptic chromosomal imbalance in patients with syndromic obesity of unknown etiology.	3 - 6 months

Secondary Outcome Measures

Name	Time	Method
candidate genes implicated in the development of obesity.	3 - 6 months
Delineation of an aetiological screening protocol in patients with syndromic obesity	3 - 6 months
prevalence of the main genetic aetiologies of syndromic obesity	3 - 6 months
Characterization of the main features evocative of subcryptic chromosomal anomalies in this population	3 - 6 months
Phenotypic description of some "new" syndromes with obesity	3 - 6 months

Trial Locations

Locations (6)

Service de Génétique de médicale - Hopital des enfants - Pellegrin; 🇫🇷 Bordeaux, France

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

Département de Génétique Médicale Centre de référence anomalies du développement Centre de compétence maladies osseuses constitutionnelles Hôpital Arnaud de Villeneuve CHRU Montpellier; 🇫🇷 Montpellier, France

Département de Génétique Hôpital Robert DEBRE Centre de Référence Maladies Rares "Anomalies du Développement & Syndromes Malformatifs"; 🇫🇷 Paris, France

Génétique Médicale HOPITAL DEBROUSSE HCL; 🇫🇷 Lyon, France

Hopital des Enfants, CHU de Toulouse; 🇫🇷 Toulouse, France