Gastroenterology and Hepatology from Bed to Bench

Abstract

Aim: To investigate the ATP7B gene in ethnically different Iranian patients with Wilson disease.

Background: Copper transporting beta polypeptide, ATP7B or WND gene is predominantly expressed in liver and has been identified as the defective gene. WND gene is located on Chr13q14.3 and consists of 21 expressed exons.

Patients and methods: Diagnosis of WD was verified according to the biochemical characterizations including serum ceroluplasmin (<0.2g/l), 24-hour urine copper after challenging by D-penicillamine (>25mmol/24h), liver copper (>250µg/g dry weight), Kayser-Fleischer rings, Cu-ATPase activity, and liver and brain imaging features. A total of 70 patients aged 5-40 years, were included. Patients were classified in three different categories; hepatic, neurologic and combined based on their clinical presentations. Bi-directional sequencing was performed using the ABI 3130xl, Genetic analyzer (Applied-Biosystem).

Results: Totally, 12 different mutations have been found in 18 patients with Wilson's disease. Of these, T788I, 2803-2805 ACG>-TG, 2532delA and H1069N were novel mutations. Meanwhile, we have found 4 polymorphisms.

Conclusion: Mutations are highly distributed among the different exons of ATP7B gene in Iranian patients with WD.