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 Study of the Liver (AEEH). We evaluated the genetic data of the patients and the differences between regions and hospitals.

Method: Multicentric observational study from the WD Registry after the first year.

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 registered, the majority in less than 4 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, 3 in more than 5 patients: p.Leu708Pro (24 patients), p.Met645Arg and p.His1069Gln (6 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 of them 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 test 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 diagnosis/screening tailored strategies.