Abstract
OBJECTIVE: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity. Data regarding MC4R mutations in Turkish subjects are limited. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents. METHODS: MC4R was sequenced in 47 consecutive morbidly obese children and adolescents (28 girls and 19 boys, aged 1-18 years) who presented during a one-year period. Inclusion criterion was a body mass index (BMI) ≥120% of the 95th percentile or ≥35 kg/m2. Patients with chronic diseases, Cushing syndrome, hypothyroidism, or suspected syndromes that could cause obesity were excluded. Onset of obesity was before age 10 years in all subjects. RESULTS: Mean age was 13.2±4.1 years, age at onset of obesity 5.1±2.1 years, height standard deviation (SD) score 1.21±0.93, BMI 40.0±8.8 kg/m2, and BMI SD score was 2.72±0.37. One novel (c.870delG) and two previously reported (c.496 G>A, c.346_347delAG) mutations were found in four (8.5%) obese children and adolescents. The novel mutation (c.870delG) was predicted to be a disease-causing frame-shift mutation using in silico analyses. Fasting glucose and lipid levels of the patients with MC4R mutation were normal, but insulin resistance was present in two of the subjects. Six more individuals with MC4R mutation (1 child, 5 adults) were detected following analyses of the family members of affected children. CONCLUSION: MC4R mutations are frequently found in morbid obese Turkish children and adolescents.