title: Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: association with liver disease.
abstract: OBJECTIVE
  To determine whether any correlation exists between the phenotype and genotype of 2 Lebanese families with members affected with Wilson disease (WD).
  
  
  BACKGROUND
  WD is an autosomal-recessive disorder of copper transport with significant phenotypic diversity. Most patients are compound heterozygous making it difficult to establish a clear link between phenotype and genotype.
  
  
  METHODS
  We investigated 14 members from 2 Lebanese families (H and Z) with 5 members affected with WD. Mutation analysis of the ATP7B gene, and clinical assessments were carried out for both families. We also performed a literature search retrieving reported phenotypes of all patients homozygous to mutations in any of the 21 exons of the ATP7B.
  
  
  RESULTS
  Patients of the H and Z-families were found homozygous for the respective Asn1270Ser and Pro1273Leu mutations in the adenosine triphosphate (ATP) hinge region of exon 18. Of the healthy members, 6 were heterozygous and 3 had normal sequences. Clinically, 4 patients had liver cirrhosis and 1 had asymptomatic transaminitis. One of the patients also had neurologic symptoms. Screening the literature for patients homozygous for mutations in the ATP hinge region identified 25 patients including ours. The overall prevalence of the hepatic phenotype among patients homozygous for mutation in exon 18 was 80% and was significantly higher than those in exons 7, 14, and 21.
  
  
  CONCLUSIONS
  We hereby report the association of liver disease with homozygous mutations in the conserved ATP hinge region of exon 18 of the ATP7B gene.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Kassem
authors.initials: K
authors.lastname: Barada
authors.forename: Mazen
authors.initials: M
authors.lastname: El-Atrache
authors.forename: Ihab I
authors.initials: II
authors.lastname: El-Hajj
authors.forename: Khaled
authors.initials: K
authors.lastname: Rida
authors.forename: Jida
authors.initials: J
authors.lastname: El-Hajjar
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Mahfoud
authors.forename: Julnar
authors.initials: J
authors.lastname: Usta
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D000073840:Copper-Transporting ATPases; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D007861:Lebanon; D008107:Liver Diseases / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D027682:Cation Transport Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases