Abstract
Wilson disease (WD), a disorder of copper metabolism is caused by mutations in the ATP7B gene, a copper transporting ATPase. In the present study we describe a novel mutation in exon 9 of the ATP7B gene. The ATP7B gene was analyzed for mutations by denaturing HPLC and direct sequencing. DNA from 100 healthy blood donors from the same geographic area was examined as control. Sixteen (7.4%) out of the 216 patients diagnosed with WD in Austria carried the newly identified 2447+1G>T(c.2448G>T) point mutation in exon 9 (4 male, age: 19 (6–30) years, median (range)). One patient was homozygous for 2447+1G>T(c.2448G>T). Thirteen patients were compound heterozygotes (p.H1069Q(c.3207C>A)/2447+1G>T(c.2448G>T) (N=6), P539L/2447+1G>T(c.2448G>T) (N=3), each one G710S/2447+1G>T(c.2448G>T), P767P(2299insC)/2447+1G>T(c.2448G>T), W779G/2447+1G>T(c.2448G>T), T1220M/2447+1G>T(c.2448G>T)). In two patients no second mutation was identified. Interestingly, all but three of the patients originated within a distinct geographical area in Austria. Eleven patients presented with hepatic disease, 3 patients with neurological disease and 2 were asymptomatic sisters of an index case. A liver biopsy was available in 14 patients. Three patients showed advanced liver disease with liver transplantation for acute hepatic failure in two. The remaining patients had only mild histological changes, most commonly steatosis. Chronic hepatitis was described in five patients. Kayser–Fleischer ring was present in five patients. None of the 100 healthy controls carried the mutation. We describe a novel mutation in the ATP7B gene, occurring in patients originated from a distinct geographical area in Austria associated with a variable course of the disease.
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16 June 2021
A Correction to this paper has been published: https://doi.org/10.1038/s10038-021-00918-w
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The original version of this article unfortunately contained a mistake. In the article, we described a “new” ATP7B variant (p.R816S) as a common mutation in Upper Austria, mistakenly considering the last 3 nucleotides of exon 9 to code for Arginine. In fact, the third nucleotide is the first of the adjacent intron. Reanalysis of the sample by NGS showed that this variant was in fact 2447+1G>T. This variant is listed as likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/).
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Hofer, H., Willheim-Polli, C., Knoflach, P. et al. Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study. J Hum Genet 57, 564–567 (2012). https://doi.org/10.1038/jhg.2012.65
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DOI: https://doi.org/10.1038/jhg.2012.65
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