Silent but significant: Functional elucidation of a synonymous ATP7B mutation in Wilson's disease pedigrees.

Introduction: Wilson's disease (hepatolenticular degeneration) is a common hereditary neurological disorder. Early diagnosis, particularly the widespread implementation of genetic testing and timely intervention, is crucial for improving the prognosis of this disease. However, limited data exist on genotype-phenotype correlations, thereby impeding accurate early clinical diagnosis. Methods: Whole-exome sequencing was performed on the proband and family members to detect genetic variants associated with the clinical phenotype. Bioinformatics tools (HSF, SpliceAI and ESEfinder 3.0) were used to predict the impact of mutations on the splicing function of precursor mRNA. The Results: Whole-exome sequencing of the proband identified a synonymous variant c.2145C>T (p. Tyr715=) and a pathogenic frameshift mutation c.2304dupC (p. Met769Hisfs*26) in the Conclusion: The compound heterozygous variants (c.2145C>T and c.2304dupC) in ATP7B likely synergistically contribute to the proband's abnormal clinical phenotype, aligning with the recessive inheritance pattern of Wilson's disease.