Screening Mutations on Exons 8,12,13,14 and 17 of ATP7B Gene By DNA Sequencing on Patients with Wilson Disease

ABSTRACTSCREENING MUTATIONS ON EXONS 8, 12, 13, 14 and 17 OF ATP7BGENE BY DNA SEQUENCING ON PATIENTS WITH WILSON DISEASEÖZLENEN Ş MŞEKAccumulation of excess copper in the body will cause Wilson Disease(WD).Depending on the copper accumulation level the symptoms arise in various organs.Copper processed in the liver can not secrete via biliary excretion. WD is mainlyinitiated as liver damage in the childhood. In the advanced ages liver, nervoussystem, eyes and kidneys have damages due to excess copper. WD can be fatal if itis not cured at early ages.It is a hereditary autosomal recessive disorder.Theresearches demonstrate that WD carrier frequency in the world is 1 in 90 andapproximately has incidence of 1/30000.In our research, mutations screened in 50 individuals members of 26 unrelatedfamilies. Exons 8, 12, 13, 14 and 17 of ATP7B gene were amplified by PCR from thegenomic DNA that extracted from individuals. The PCR product belong to eachexons sequenced by using both forward and reverse primers and the obtained datafrom sequencing result were evaluated and mutations screened.Five different mutations and additionally one new mutation are observed onexon eight of six unrelated families; one mutation and one SNP is found on exon 12of 23 unrelated families; two different mutations and three SNPs are observed onexon 13 of nine unrelated families; two different mutations one is new, observed onexon 14 of eight unrelated families; one new mutation is observed on exon 17 in onefamily. As a cumulative observation the mutations and SNPs on five exons out of 21exons of ATP7B gene were defined. The results covered %96.15 of the patientsmembers of 26 unrelated families.In conclusion, ATP7B mutations in WD defined according to internationalstandards in the laboratory of Medical Biology and Genetics, School of Medicine ofDokuz Eylül University.The data evaluated with the clinicians to confirm the WD andadditionally the members of the families who have no symptoms but have themutations, have a chance to get the preventive therapy. Defined new mutationscontribute to the literature.The relationship between patient?s clinical findings andmutation analysis assist the improvement of protective medicine.Key Words:Wilson Disease,ATP7B gene,mutation,copper,SNP2