A novel splice-site allelic variant is responsible for Wilson Disease in an Omani family

Objectives: The objective of this study was to characterise Wilson's Disease (WD) [OMIM 277900] genetically and test for allelic variants in the copper transport gene (ATPase, Cu ⁺⁺ transporting, beta polypeptide, ATP7B) responsible for the disease in an Omani family. Methods: Three index patients from an Omani family had been previously diagnosed with WD. All three patients suffered neurological symptoms and signs. Forty-six relatives in the family were screened for WD. Eleven more individuals were positive, but asymptomatic. Results: Thirteen non-disease-causing allelic gene variants, described previously, were identified in the ATP7B gene from 46 family members. A putative novel disease-causing splice-site variant (c.2866-2A>G), which has not been reported previously, was detected in this family. It is located upstream of exon 13 which encodes part of transmembrane copper channel (Ch/Tm6). Reverse transcription polymerase chain reaction was used to amplify a complementary DNA (cDNA) fragment containing exons 12, 13 and 14. Exon 13 was entirely skipped from the transcript which probably would result in a defective ATP7B protein. Conclusion: A new ATP7B splice-site allelic variant, found among the 14 WD patients segregated with the disease in a recessive manner, suggests it is a disease-causing variant.