Objective: The objective of our study is to elucidate the prevalence of heterozygous ATP7B mutation in patients with movement symptoms. We aim to determine whether ATP7B heterozygous mutation is more prevalent with patients with symptoms such as ataxia, which may suggest that ATP7B can contribute to overt movement symptoms even in heterozygous carriers.

Background: The sentence is stating that the ATP7B gene is significant not just within the realm of movement disorders, but also across various areas of medicine. This is due to the wide range of symptoms caused by homozygous mutations in this gene, Wilson’s disease. Due to the autonomic recessive nature of the disease, heterozygous mutation of ATP7B gene is not usually a cause for concern. However, as in most genetic disorders regarding metabolic processes, even carriers of this mutated enzyme-encoding gene may be hypothesized to show minor to significant movement symptoms.

  In this study, we aim to compare the prevalence of heterozygous ATP7B mutation among patients with movement symptoms with those of the general population to determine whether it is higher among the diseased.

Method: We conducted a single center case-control study of 347 patients who were tested for NGS panels that include the ATP7B gene for movement symptoms such as ataxia, parkinsonism and dystonia between October, 2019 and July, 2023. These tests were ordered by neurologists for patients under suspicion for genetic etiology of movement symptoms.

Results: Among the 347 Korean patients who underwent NGS panels, 10 (2.8%) patients had heterozygous mutation for ATP7B. Among the ten patients, five patients had ataxia (50%), three had dystonia (30%), and two had parkinsonism (20%), with ataxia as the most common symptom. The prevalence of 10 carriers among 347 (2.8%) for the population with movement symptoms was significantly higher than that of the Korean general population (0.0067). 

Conclusion: Although ATP7B mutation carriers are previously known only to have negligible significance of copper metabolism, generally remaining asymptomatic, the prevalence of carriers were significantly higher than that of the general population. Therefore, we hypothesize that even heterozygous mutation of ATP7B may play a pathophysiologic role in complex motor regulation, resulting in movement symptoms such as ataxia.

References: Journal of Human Genetics (2017) 62, 815–818

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-heterozygous-atp7b-mutation-in-patients-with-movement-symptoms/