P08 Genetic variability in Wilson's disease- real world results from London, UK. (20th September 2022)

• Record Type: Journal Article
• Authors: Yin, James Liu; Allouni, Sammi; Bomford, Adrian; Ala, Aftab
• Is Part Of: Gut. Volume 71(2022)Supplement 3
• Page Start: A36
• Page End: A37
• Publication Date: 2022-09-20
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2022-BASL.59
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: Wilson's disease (WD) has been shown to have more than 600 different variants causing abnormal function of the ATP7B peptide. There is wide global diversity in these variants with different variants appearing to be more prominent in certain geographical areas and populations than others. London, UK is one of the largest, ethnically diverse cities in Western Europe with a growing population of over 9 million. It receives over 100, 000 international migrants a year, with the largest proportions from the European Union and Indian Subcontinent. We aimed to review the genetic results at Kings College Hospital, London from patients with abnormal WD genetics and compare this to known global distribution. Methods: We retrospectively collected data on all WD genetic testing done at KCH since becoming one of the national testing centres (2015-present).We further extracted information on specific cDNA, protein change and zygosity status. We subsequently used WilsonGen, (Comprehensive genomic variant resource) which has compiled a large database of variants, (2267 entries currently) to compare whether our variants were unique or previously documented. Results: We identified 207 patients tested for WD, 30 homozygous, 91 compound heterozygotes and 86 heterozygotes (Mean 28.9 years, range 4–70). Within this, there were 113 different variants identified. The most common was His1069Gln (11%), followed by Cys271Ter (3.6%), Met769Val (3.6%) and Ser1365fs (3.2%). On comparison with the WilsonGen database we found that 44 variants were not listed on their records (38.9%). We had ethnicity data accessible for 137 patients, 49% were documented as unspecified and the remaining were; Caucasian (35%), Indian Subcontinent (7%), Middle Eastern (4%), Black/Caribbean (3%), Chinese (1%) and other (<1%). Conclusion: Our results demonstrate significant genetic variation in London with the most common mutation only accounting for 11% of the overall total. As genetic testing becomes a more utilized tool in furthering diagnostic pathways we need to understand that this variation may have significance. The importance of ATP7B genetic variation is yet to be fully understood and characterised with respect to the pathogenesis of WD. Within our cohort, the presence of novel variants was 39% which is a significant portion and higher than previously reported UK data (27% Coffey et al). Considering the wide spread of variation including novel variants, specific mutations have not been shown to confer benefit thus far and therefore further understanding of its significance is needed.