novel splice-site allelic variant is responsible for wilson disease in an Omani family

ABSTRACT

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. 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. 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. 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