Microarray Analysis in Syndromic Obesity (REMOB)

• Evaluation of the prevalence of cryptic chromosomal imbalance in patients with syndromic obesity of unknown etiology. [ Time Frame: 3 - 6 months ]
  

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

Genetic: Clinical examination and blood sampling for biological and genetic analysis

Clinical examination and precise description of the phenotype (questionnaire)

• Standardized screening with :
• radiological (hands, feet, spine ; and renal ultrasonography)
• biological (hormonal, metabolic, and "basic" genetic investigations (karyotype, FISH 22q11.2, Fragile X, and other depending on the clinical data))

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.