Genetic map of Wilson disease in Spain - A great tool to improve diagnosis and screening

Abstract

Background: a National Registry for Wilson disease (WD) was recently started by the Spanish Association for the Study of the Liver (AEEH). We evaluated the genetic data of the patients and the differences between regions and hospitals.

Methods: a multicentric observational study from the WD Registry after the first year was carried out.

Results: patients from 30 hospitals, in 13/17 Spanish regions (covering 80 % of population) were included. Genetic data were available for 260/320 patients. More than 130 mutations in the ATP7B gene were reported, the majority in less than four alleles, being most prevalent p.Met645Arg (20 % alleles, mainland and the Canary Islands), p.Leu708Pro (16.5 %, Canary Islands) and p.His1069Gln (8.3 %, mainland). Only 15 mutations occurred in homozygosis, three in more than five patients: p.Leu708Pro (24 patients), p.Met645Arg and p.His1069Gln (six patients each). Genetic data availability ranged from 0-100 % among regions; similarly, the difference among hospitals within a region was larger than 50 %. Without a genetic test, up to 45 % of patients would not have reached Leipzig score > 3. In screening cases, genetics was used in 45/58 (78 %); without genetics, two thirds would not have reached a Leipzig score > 3 (33/49).

Conclusion: here we present the first genetic map of WD in Spain. The use of genetic tests was highly heterogeneous, being higher in screening cases. Although a large variability of mutations was found, regional characteristics indicated that screening for a limited number of exons (6, 8, 10, 14 or 17) would detect more than 50 % of alleles in a given region, thus enabling the design of better tailored diagnosis/screening strategies.