Genetic Variants and Mutation Patterns in Pediatric Hyperthyroidism: Insights from Canonical Correlation Analysis

Abstract

Background: Genetic mutations play a pivotal role in the development and progression of hyperthyroidism in children. Different mutation types—including missense, nonsense, synonymous, and splice-site changes—exert variable biological effects, but their collective contribution remains underexplored.

Objective: This study aimed to identify representative mutant genes and single nucleotide polymorphisms (SNPs) associated with pediatric hyperthyroidism and to examine how mutation types interact with these genomic features through canonical correlation analysis (CCA).

Methods: Whole-exome sequencing was performed in 39 children with hyperthyroidism. From 144 hyperthyroidism-related genes and 1,221 SNPs, redundant and low-variance features were eliminated. Representative genes and SNPs strongly correlated with mutation types were selected, and CCA was used to explore associations between mutation classes, genes, and SNPs.

Results: Twenty-three genes and eight SNPs emerged as highly informative. Genes such as KANK1, CGA, TPO, and TSHR demonstrated strong tendencies toward specific mutation types, with KANK1 exerting the largest gene-level effect. Among SNPs, g.44651599T>C showed the greatest influence on mutation profiles. Overall, missense and synonymous variants were most impactful in shaping the mutational landscape.

Conclusion: Pediatric hyperthyroidism demonstrates structured relationships between specific genes, SNPs, and mutation types. KANK1, CGA, and g.44651599T>C may represent crucial drivers of disease biology. Understanding these associations may facilitate refined molecular diagnostics and targeted interventions in children.