Author/Authors :
Zali, Narges Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Mohebbi, Reza Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Esteghamat, Sahar Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Chiani, Mohsen Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Montazer Haghighi, Mahdi Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Hosseini-Asl, Mohammad-Kazem Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Derakhshan, Faramarz Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Mohammad-Alizadeh, Amir- Houshang Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Malek-Hosseini, Ali Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran , Zali, Mohammad Reza Research Centre for Gastroenterology and Liver Diseases - Shahid Beheshti University of Medical Sciences, Tehran
Abstract :
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.
