Clinical trial NCT01043198: Microarray Analysis in Syndromic Obesity
Official title: Phenotypic Characterization and Array CGH Analysis in Patients With Syndromic Obesity of Unknown Etiology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mental Retardation
Syndromic Obesity
Keywords: CGH array technology
mental retardation
chromosomal abnormalities
syndromic obesity
obesity
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2010-01-06
Enrollment: 90
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of the prevalence of cryptic chromosomal imbalance in patients with syndromic obesity of unknown etiology.
timeFrame: 3 - 6 months
Secondary outcomes:
measure: prevalence of the main genetic aetiologies of syndromic obesity
timeFrame: 3 - 6 months
measure: Characterization of the main features evocative of subcryptic chromosomal anomalies in this population
timeFrame: 3 - 6 months
measure: Phenotypic description of some "new" syndromes with obesity
timeFrame: 3 - 6 months
measure: candidate genes implicated in the development of obesity.
timeFrame: 3 - 6 months
measure: Delineation of an aetiological screening protocol in patients with syndromic obesity
timeFrame: 3 - 6 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Service de Génétique de médicale - Hopital des enfants - Pellegrin
city: Dijon
country: France
facility: Centre de Génétique Hôpital d'Enfants CHU de Dijon
city: Lyon
country: France
facility: Génétique Médicale HOPITAL DEBROUSSE HCL
city: Montpellier
country: France
facility: Département de Génétique Médicale Centre de référence anomalies du développement Centre de compétence maladies osseuses constitutionnelles Hôpital Arnaud de Villeneuve CHRU Montpellier
city: Paris
country: France
facility: Département de Génétique Hôpital Robert DEBRE Centre de Référence Maladies Rares "Anomalies du Développement & Syndromes Malformatifs"
city: Toulouse
country: France
facility: Hopital des Enfants, CHU de Toulouse
Study officials:
affiliation: University Hospital Bordeaux, France
name: Marie-Ange DELRUE, MD
role: PRINCIPAL_INVESTIGATOR
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