Dataset Information

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

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.

SUBMITTER: Zali N

PROVIDER: S-EPMC3269057 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zali Narges N Mohebbi Seyed Reza SR Esteghamat Sahar S Chiani Mohsen M Haghighi Mahdi Montazer MM Hosseini-Asl Seyed Mohammad-Kazem SM Derakhshan Faramarz F Mohammad-Alizadeh Amir-Houshang AH Malek-Hosseini Seyed-Ali SA Zali Mohammad Reza MR

Hepatitis monthly 20111130 11

<h4>Background</h4>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.<h4>Objectives</h4>We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.<h4>Patients and methods</h4>Genomic DNA was extracted from patients with Wilson disease. T ...[more]

PMID: 22308153

Similar Datasets

Project description:AIM:To determine the mutational characterization of P-type ATP7B gene and to explore the correlation of ATP7B genotype to phenotype in Chinese patients with Wilson disease (WD). METHODS:Seventy-five patients with WD from 72 no-kinship families, 44 males and 31 females, were enrolled in this study. The age of onset ranged from 4 to 39 years, <=18 years in 72 patients. Some exons of ATP7B gene mutations were analyzed in patients with WD by using biochemical methods, polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and DNA sequence analysis. A total of 778 coding regions were identified with restriction enzyme Msp I. The activity of Cu-ATPase was assessed by measuring inorganic phosphorus. RESULTS:Sixty-six of 75 patients (88%) had with hepatic manifestations, 39 of them had only hepatic manifestations, 27 patients had hepatic and neurological manifestations or other symptoms at the same time (16 patients had associated neurological manifestation, 3 patients had osteopathy, 8 patients had other symptoms). Eight of the 75 patients (10.7%) had only neurological symptoms, one patient (5 years old) had no symptom. Twelve changing patterns were detected in ATP7B gene by DNA sequencing, including seven mutations (R778L, C656X, G943D, V1140A, V1106I V1216M and 1384del17), six polymorphisms (IVS4-5t/c, A2495G, C2310G, IVS18+6c/t and IVS20+5a/g). R778L occurred in 49/66 patients (74%) with hepatic manifestations, homozygosis of R778L in 16 patients, heterozygosity of R778L in 33 patients. V1106I mutation of ATP7B gene occurred in 2 patients with delaying onset of clinical symptoms. Cu-ATPase activity of three patients with known mutations (R778L/V1106I/A2495G, R778L/V1216M and R778L/R778L) were determined, and the activity of Cu-ATPase was decreased by 44.55%, 88.23% and 69.49% respectively. CONCLUSION:1384del17bp is a novel mutation found in WD patients. R778L is the most common mutation of ATP7B gene. There is a correlation between R778L and hepatic manifestations in WD patient.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure