title: The same haplotype for two unrelated Wilson disease patients with new ATP7B mutation.
abstract: BACKGROUND
  Wilson disease is a rare autosomal recessive disorder of copper metabolism caused by mutation in the ATP7B gene. The combination of markers (such as SNPs) on a single chromosome can be used to understand the structure of haplotype in the human genome, in which provide notable information on the origin of the mutation in human genetic disorders. The purpose of this study was to determine a haplotype analysis of two unrelated Wilson disease patients with the same missense mutation, c.2335T>G (g.58164 T>G) in exon 8.
  
  
  METHODS
  DNA was prepared from two patients with the c.2335T>G mutation, their first-degree relatives, and 50 selected homozygous individuals from consanguineous marriage for eight SNPs around this particular ATP7B mutation. PCR was performed for SNPs of exons 4 (g.47964 C>T), 5 (g.51482G>A), 6 (g.54622A>G), 7 (g.56255G>A), 9 (g.59042G>T), 11 (g.66363G>A), 13 (g.70004 G>C), and 14 (g.72244 A>G), which are located in upstream and downstream of this mutation. Then, restriction fragment length polymorphism (RFLP) for these eight SNPs was designed and performed using eight different restriction enzymes.
  
  
  RESULTS
  Eight different haplotypes were found in the present study and the patients with the same missense mutation had the same haplotype. The most prevalent haplotype in 100 normal studied ATP7B alleles was the same as reference haplotype (C G A G T G G G A) for ATP7B gene (NG_008806.1).
  
  
  CONCLUSIONS
  As these two geographically separated families with the same mutation had the same haplotype, we concluded that this mutation possibly had the same origin in this population.
authors.affiliation: Department of Medical Genetics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran, Departments of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran. mfardaei@sums.ac.ir.
authors.forename: Hassan
authors.initials: H
authors.lastname: Dastsooz
authors.affiliation: Shiraz Transplant Research Center, Gastroenterohepatology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Seyed Mohsen
authors.initials: SM
authors.lastname: Dehghani
authors.affiliation: Department of Medical Genetics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran Departments of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Fardaei
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D006239:Haplotypes / Q000235:genetics*; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases