A novel mutation in the ATP7B gene causing hepatolenticular degeneration in a Chinese family: A case report.

Abstract

Hepatolenticular degeneration (Wilson disease) is an autosomal recessive monogenic disorder caused by mutations in the ATPase copper transporting beta (ATP7B) gene located on human chromosome 13. This gene encodes a copper-transporting P-type ATPase (ATP7B). Recent studies have revealed that the ATP7B gene is predominantly affected by a few hotspot mutations, with the His1069Gln mutation in exon 14 accounting for 50 to 80% of cases. In China, the Arg778Leu mutation in exon 8 is the most prevalent. However, the discovery of novel mutant genes persists. A 56-year-old Chinese female was referred to our hospital with a liver injury and cirrhosis. Her parents, 2 younger brothers, and children exhibited no signs of liver function impairment. Whole-exome sequencing was conducted on the proband's genomic DNA, and Sanger sequencing was performed on 6 family members for first-generation verification. We identified a novel c.3715G > T (p.Val1239Phe) variant mutation in the ATP7B gene in the patient. The ATP7B c.3715G > T (p.Val1239Phe) variant is predicted to impact the copper transport P-type ATPase. When combined with another mutant gene to form a compound heterozygous mutation, it can lead to hepatolenticular degeneration. This discovery broadens the range of pathogenic genes in the ATP7B gene.