title: Gene mutations in Wilson disease in Egyptian children: report on two novel mutations.
abstract: OBJECTIVE
  Wilson disease (WD) is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase (ATPase) encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation (p.H1069Q) in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group.
  
  
  METHODS
  Direct DNA sequencing was applied to exons (13, 14, 18, and 19) of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families (three families).
  
  
  RESULTS
  We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution (p.A1074A) in 16% of patients and the other was predicted to be missense disease-causing mutations (p.T1076I) in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients.
  
  
  CONCLUSIONS
  Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations.
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Fatma A
authors.initials: FA
authors.lastname: El-Mougy
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Sahar A A
authors.initials: SA
authors.lastname: Sharaf
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt. Electronic address: marwaelsharkawy@yahoo.com.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Elsharkawy
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Iman A
authors.initials: IA
authors.lastname: Mandour
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Riham A
authors.initials: RA
authors.lastname: El-Essawy
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Eldin
authors.affiliation: Department of Pediatrics, Cairo University Pediatric Hospital, Cairo, Egypt.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Helmy
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Dina H
authors.initials: DH
authors.lastname: Soliman
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Lamia H
authors.initials: LH
authors.lastname: Selim
authors.affiliation: Department of Clinical and Chemical Pathology, Kasr Al-Aini Hospital, Cairo University, Cairo, Egypt.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Sharafeldin
authors.affiliation: Department of Pediatrics, Cairo University Pediatric Hospital, Cairo, Egypt.
authors.forename: Engy A
authors.initials: EA
authors.lastname: Mogahed
authors.affiliation: Department of Pediatrics, Cairo University Pediatric Hospital, Cairo, Egypt.
authors.forename: Hanaa M
authors.initials: HM
authors.lastname: El-Karaksy
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D000073840:Copper-Transporting ATPases; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D027682:Cation Transport Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; DNA sequencing; Mutations; Wilson disease (WD)