Detection of Mutations in Exon 10 and 13 of ATP7B Gene among Iraqi patients with Wilson Disease

copper metabolism due to mutations in copper transport gene ATP7B resulting in hepatic and neuropsychiatric manifestation. The aim of this study is to investigate the extent to which mutations in gene ATP7B involved in development of WD and assessment of parameters related to copper metabolism in patients with Wilson disease. Accordingly, blood samples were obtained from 35 patients with WD (20 male and 15 female) with a mean age of 9.12 years and age range of 5 – 40 years old Other 10 apparently, healthy individuals were also included. The serum level of ALT, AST, ALP, and Bilirubin were investigated which were (132.14±23.12 U/L, 96.93±11.21 U/L, 184.29±48.45 U/L and 3.6±1.13 mg/dl) respectively that differed significantly from their counter control groups. Serum level of copper among WD patients of ranged from (78 –214 mg/dl) with average of (127.18±64.432 µg/dl), this average does not differ significantly from that of control groups. A total of 70 alleles belong to 35 WD patients and other 20 alleles belong
to healthy individuals have been examined for mutations in the exon 10 and exon 13 of ATP7B gene. Seven different mutations have been recorded. These includes three nucleotide polymorphisms (SNPs) :
Lys832Arg, Pro840Leu and Thr991 Thr with 22.86% , 25.71% and 4.29% frequencies respectively; two point mutations : Ala1003 Val and Lys1010Arg which had 8.57% and 11.42%  frequencies respectively and
two frameshift mutations: c.2977-2978insA and c.2457delA with frequency of 24.29% and 27.14% frequency among WD patients. These data strongly indicate that both c.2519C>T polymorphism and the
frameshift mutation c.2977-2978insA could be exploited in the development of molecular diagnosis of WD. However, further studies are required to find out the most prevalent mutations in other exons.