Wilson disease associated with a novel variant in the ATP7B gene
TL;DR
A novel deletion variant in a Wilson disease patient harboring compound heterozygous variants in ATP7B is identified, expanding the known spectrum of pathogenic ATP7B variants.
Abstract
Introduction Wilson disease is an autosomal recessive monogenic disorder caused by mutations in the copper-transporting P-type ATPase beta gene (ATP7B) located on human chromosome 13. This gene encodes copper-transporting P-type ATPase. This article reports a case of Wilson disease with a novel ATP7B deletion variant. Case report We report a case of Wilson disease in a Chinese female patient. Cirrhosis was detected during routine examination at the age of 24 and was accompanied by reduced serum ceruloplasmin levels. At the age of 27, she gradually developed tremors and dystonia. Brain magnetic resonance imaging (MRI) revealed abnormal signals in the basal ganglia. Genetic testing for ATP7B was performed on the patient and her family members. Results Genetic testing revealed that the patient harbored compound heterozygous variants, including a previously reported c.1543+40G>A variant and a novel c.837delT variant in exon 2, which has not been previously reported. The c.1543+40G>A variant is registered in the ClinVar database with conflicting interpretations of pathogenicity (likely pathogenic/likely benign), The c.837delT variant is predicted to result in a frameshift (p.Ile279Metfs*5), introducing a premature termination codon, and is thus likely to impair the function of the copper-transporting P-type ATPase. Conclusion We identified a novel deletion variant in a Wilson disease patient harboring compound heterozygous variants in ATP7B. This finding expands the known spectrum of pathogenic ATP7B variants.