Screening of non-syndromic early-onset child and adolescent obese patients in terms of and gene variants by next-generation sequencing.

Objectives: Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes ( and ) in children and adolescents who had severe, non-syndromic early onset obesity.

Methods: Next-generation sequencing of all exons in and was performed in 154 children and adolescents with early onset severe obesity obesity.

Results: Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in gene (10/154 patients; 6.5%), five different variants in gene (four of them were heterozygous and one of them was homozygous) (6/154 patients; 3.9%) and four different homozygous variants in gene (3/154 patients; 1.9%) were described. However, no variants were detected in the LEP gene. The most common pathogenic variant was c.496G>A in gene, which was detected in four unrelated patients. Six novel variants (6/15 variants; 40%) were described in seven patients. Four of them including c.233C>A and c.752T>C in gene and c.761dup and c.1221dup in gene were evaluated as pathogenic or likely pathogenic.

Conclusions: In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in gene is highly prevalent in early-onset obese patients.