J. Clin. Endocrinol. Metab. 2015 May;100(5):E757-66
PubMed ID: 25751111
Abstract
CONTEXT: Infrequent mutations have been reported in the leptin receptor (LEPR) gene in humans with morbid obesity and endocrine disorders. However LEPR mutations are rarely examined in large populations from different ethnicities in a given country.
OBJECTIVE: We estimated the prevalence of LEPR mutations in French patients with severe obesity and evaluated mutated patients’ phenotype.
DESIGN AND PATIENTS: We sequenced the LEPR gene in 535 morbidly obese French participants. We conducted clinical investigations to determine whether individuals with a novel shared mutation display particular characteristics relative to obesity history, body composition, hormonal functions, and the outcome of bariatric surgery.
RESULTS: We identified 12 patients with a novel LEPR mutation (p.C604G, p.L786P, p.H800_N831del, p.Y422H, p.T711NfsX18, p.535-1G>A, p.P166CfsX7). Six unrelated subjects were carriers of the p.P166CfsX7 mutation leading to deletion overlapping exons 6 to 8. All subjects originated from Reunion Island (France). Their clinical features (severe early-onset obesity, food impulsivity, and hypogonadotropic hypogonadism) did not differ from other new LEPR mutation carriers. Results concerning weight loss surgery were inconsistent in homozygous LEPR mutation carriers. Heterozygous LEPR mutation carriers exhibited variable severity of obesity and no endocrine abnormality.
CONCLUSION: Among seven newly discovered LEPR mutations in this French obese population, we identified a LEPR frameshift mutation shared by six subjects from Reunion Island. This observation suggests a founder effect in this Indian Ocean island with high prevalence of obesity and supports a recommendation for systematic screening for this mutation in morbidly obese subjects in this population.