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