Melanocortin-4 receptor gene mutations in obese Slovak children

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Non-syndromic monogenic obesity frequently results from mutations in the Melanocortin-4 receptor (MC4R) gene.
• MC4R mutation prevalence varies significantly across different countries, ranging from 1.2% to 6.3% in obese children.

Purpose of the Study:

• To investigate the prevalence of MC4R mutations in obese children in Slovakia.
• To compare these findings with prevalence rates in other European populations.
• To characterize the phenotype of MC4R mutation carriers.

Main Methods:

• DNA analysis using direct Sanger sequencing of MC4R coding exons and intron/exon boundaries.
• Study included 268 unrelated Slovak children and adolescents with obesity (BMI > 97th percentile) and early onset (mean age 4.3 years).

Main Results:

• Two previously described heterozygous loss-of-function MC4R variants (p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands.
• One obese and one lean adult family relative carried the p.Ser127Leu variant.
• No loss-of-function variants were detected in lean control individuals.
• The prevalence of MC4R loss-of-function variants in obese Slovak children was 0.7%, one of the lowest reported in Europe.

Conclusions:

• The prevalence of MC4R loss-of-function variants in obese Slovak children is low compared to other European populations.
• This study contributes to understanding the geographical variation in MC4R mutation frequencies related to monogenic obesity.