title: A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations.
abstract: Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.
authors.affiliation: Section of Neurology, Department of Medicine, King Fahad National Guard Hospital, Riyadh, Saudi Arabia. jumahm@ngha.med.sa
authors.forename: M
authors.initials: M
authors.lastname: Al Jumah
authors.forename: R
authors.initials: R
authors.lastname: Majumdar
authors.forename: S
authors.initials: S
authors.lastname: Al Rajeh
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.forename: A
authors.initials: A
authors.lastname: Al Zaben
authors.forename: I
authors.initials: I
authors.lastname: Al Traif
authors.forename: A R
authors.initials: AR
authors.lastname: Al Jumah
authors.forename: Z
authors.initials: Z
authors.lastname: Rehana
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000073840:Copper-Transporting ATPases; D005091:Exons / Q000235:genetics; D005260:Female; D006527:Hepatolenticular Degeneration / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012529:Saudi Arabia / Q000453:epidemiology
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases