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.
Keywords: Early-Onset obesity; Exome sequencing; Genetic; Novel Variants.
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