title: A Novel Splice-site Allelic Variant is Responsible for Wilson Disease in an Omani Family.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman;
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Tobi
authors.forename: Masoud
authors.initials: M
authors.lastname: Kashoob
authors.forename: Surendranath
authors.initials: S
authors.lastname: Joshi
authors.forename: Riad
authors.initials: R
authors.lastname: Bayoumi
references.citation: Am J Hum Genet. 1997 Jun;60(6):1423-9
references.pmid: 9199563
references.citation: Am J Hum Genet. 1997 Aug;61(2):317-28
references.pmid: 9311736
references.citation: Genet Test Mol Biomarkers. 2009 Apr;13(2):185-91
references.pmid: 19371217
references.citation: Hum Mutat. 1998;12(2):89-94
references.pmid: 9671269
references.citation: Genomics. 1996 Nov 1;37(3):303-9
references.pmid: 8938442
references.citation: Am J Hum Genet. 1995 Dec;57(6):1318-24
references.pmid: 8533760
references.citation: Nat Genet. 1995 Feb;9(2):210-7
references.pmid: 7626145
references.citation: Hum Mutat. 1998;11(4):275-8
references.pmid: 9554743
references.citation: Hum Mutat. 1998;11(2):145-51
references.pmid: 9482578
references.citation: Hum Mutat. 2002 Oct;20(4):260-6
references.pmid: 12325021
references.citation: Ann Trop Paediatr. 2002 Mar;22(1):93-6
references.pmid: 11926058
references.citation: Am J Hum Genet. 1995 Jun;56(6):1315-9
references.pmid: 7762553
references.citation: Mol Genet Metab. 2005 Sep-Oct;86(1-2):277-85
references.pmid: 15967699