Zali Narges, Mohebbi Seyed Reza, Esteghamat Sahar, Chiani Mohsen, Haghighi Mahdi Montazer, Hosseini-Asl Seyed Mohammad-Kazem, Derakhshan Faramarz, Mohammad-Alizadeh Amir-Houshang, Malek-Hosseini Seyed-Ali, Zali Mohammad Reza
Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hepat Mon. 2011 Nov;11(11):890-4. doi: 10.5812/kowsar.1735143X.762. Epub 2011 Nov 30.
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.
We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.
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.
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.
Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients.
威尔逊病（WD）是一种常染色体隐性疾病。WD基因ATP7B编码一种铜转运ATP酶，参与将铜转运到血浆蛋白铜蓝蛋白中以及从肝脏排出铜。ATP7B突变会导致铜在肝脏和大脑中蓄积。
我们检测了伊朗威尔逊病患者的ATP7B突变谱。
从威尔逊病患者中提取基因组DNA。使用聚合酶链反应（PCR）扩增ATP7B基因的整个编码区，并通过直接测序进行分析。
我们在5名伊朗威尔逊病患者中鉴定出5种新突变。第一种是颠换，c.2363C>T，导致氨基酸从苏氨酸变为异亮氨酸。第二种突变是缺失，c.2532delA（Val845Ser），发生在外显子10中。第三种突变是转换突变，c.2311C>G（Leu770Leu），发生在ATP7B蛋白的TM域4中。第四种突变是颠换，（c.3061G>A）（Lys1020Lys），在外显子14中。最后，我们在外显子14中鉴定出一种颠换，c.3206C>A（His1069Asn），这导致ATP7B蛋白的ATP环结构域功能发生改变。H1069Q突变被确定为我们研究人群中最常见的突变。
基于我们的研究结果，H1069Q可能是一种生物标志物，可用于快速检测法诊断WD患者。
