There are no differences in terms of hepatic, neurological, psychiatric, or other symptoms at diagnosis between patients with Wilson disease (WD) who are positive or negative for the p.H1069Q variant, according to a new study conducted in a Finnish population.

“These results suggest that population-specific factors may partly explain the high clinical variability of Wilson’s disease,” the study authors wrote.

Read more about the genetics of WD

The paper was published in the Journal of the Neurological Sciences.

There are limited data available on the possible correlation between genotype and phenotype in WD. To shed some light on this subject, a team of researchers led by Valtteri Kaasinen, MD, PhD, from the University of Turlu in Finland, conducted a retrospective cohort study in 17 patients. Of these, 6 had a homozygous mutation in the ATP7B gene, while 11 were compound heterozygous.

The results showed that there were no differences between the 2 groups of patients in terms of the presence or absence of hepatic, neurological, psychiatric, or other symptoms at the time of diagnosis. However, patients who were homozygous were generally diagnosed earlier than compound heterozygous patients. 

The researchers also found that severe liver disease was almost exclusively associated with the p.H1069Q variant and that patients with this variant were generally diagnosed later than those without. However, there were no differences in symptoms at diagnosis between patients who were p.H1069Q positive and those who were negative.

“These findings, along with previous findings from other regions, suggest that there are also population-specific factors that explain the high clinical variability of WD,” the authors concluded.

WD is a rare genetic disease inherited in an autosomal recessive manner. It is caused by a mutation in the ATP7B gene, which codes for the copper-transporting ATPase protein. Therefore, this mutation leads to the excessive accumulation of copper in the body, causing symptoms such as hepatic dysfunction and neurological and psychiatric problems. 


Sipilä JOT, Kytövuori L, Kaasinen V. Clinical spectrum and genotype-phenotype associations in Finnish patients with Wilson’s disease. J Neurol Sci. Published online March 22, 2023. doi:10.1016/j.jns.2023.120620