Investigating genetic variants in early-onset obesity through exome sequencing: A retrospective cohort study

Objective

This study aimed to examine clinical data and analyze exome sequencing (ES) findings in children diagnosed with early-onset obesity.

Methods

We screened children presenting with severe (body mass index-standard deviation score >3) and early-onset (<7 years) obesity using ES. Participants were categorized into either the "no variant identified" group or the "variant identified" group, facilitating the exploration of correlations between clinical-demographic characteristics and genetic mutations linked to early-onset obesity. The functional implications of identified variants were assessed through in silico analyses.

Results

Of the patients, 32 (35.5 %) possessed one or more mutations in pathways associated with obesity, all of which were heterozygous and patients with more than two obesity-associated variants were more obese. This cohort included 29 novel mutations distinct to our study population, 7 previously reported pathogenic variants, two instances of uniparental disomy, and one mitochondrial hotspot mutation. Variants in the SH2B1 gene emerged as a prevalent genetic determinant of obesity within our group, accounting for 16.6 % of cases. Statistical evaluations showed no significant differences in demographic attributes between the two groups.

Conclusion

Exome sequencing proves to be an instrumental approach for uncovering new variants and broadening the spectrum of mutations in early-onset obesity among children. Concurrently, further functional studies, both in vitro and in vivo, are crucial to elucidate the contributions of these variants to obesity's pathogenesis.