Background: Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain. Objectives: We examined the ATP7B mutation spectrum in Wilson disease patients in Iran. Patients and Methods: Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing. Results: We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population. Conclusions: Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients.
Implication for health policy/practice/research/medical education:
Although a variety of mutations have been identified in the ATP7 gene in Wilson disease patients around the world, there is not enough data about it in Iranian patients. This study will provide valuable information about mutational hot spot regions of ATP7B gene in Iranian patients for the first time and may help researchers to develop specific diagnostic tests for our population. We highly recommend biologists and Gastroenterologists to study this article.
Please cite this paper as: Zali N, Mohebbi SR, Esteghamat S, Chiani M, Montazer Haghighi M, Hosseini-Asl SM, et al. Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease. Hepat Mon. 2011;11(11):890-4. DOI: 10.5812/kowsar.1735143X.762