Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease.
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.


OBJECTIVE
We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.


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.
Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Narges
N
Zali
Seyed Reza
SR
Mohebbi
Sahar
S
Esteghamat
Mohsen
M
Chiani
Mahdi Montazer
MM
Haghighi
Seyed Mohammad-Kazem
SM
Hosseini-Asl
Faramarz
F
Derakhshan
Amir-Houshang
AH
Mohammad-Alizadeh
Seyed-Ali
SA
Malek-Hosseini
Mohammad Reza
MR
Zali