Mutation analysis and characterization of alternative splice variants of the Wilson disease gene ATP7B.

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16510

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/16510

题名:	Mutation analysis and characterization of alternative splice variants of the Wilson disease gene ATP7B.
作者:	萬磊;Wan, Lei;Tsai, FJ
贡献者:	生物科技學系
日期:	2010-11
上传时间:	2012-11-23 09:14:02 (UTC+0)
摘要:	Wilson disease is a copper metabolism disorder caused by mutations in ATP7B, a copper-transporting adenosine triphosphatase. A molecular diagnosis was performed on 135 patients with Wilson disease in Taiwan. We identified 36 different mutations, eight of which were novel: five missense mutations (Ser986Phe, Ile1348Asn, Gly1355Asp, Met1392Lys, and Ala1445Pro), one deletion (2810delT) in the coding region, and two nucleotide substitutions (−133A→C and −215A→T) in the promoter region. These mutations were not observed in 100 control subjects and reduced the activity of the mutated protein by at least 50% when compared with wild-type ATP7B. In addition to exon 8, our data indicate another mutation hotspot in exon 12 where 9.62% of all mutations occurred. An alternative splice variant of ATP7B lacking exon 12 was observed in one patient who had a homozygous 2810delT mutation and very mild clinical symptoms. Clinical examination and functional characterization of alternative splice variants of ATP7B lacking exon 12 showed that they retained 80% of their biological activity. The 2810delT mutation increased the expression of these variants, which may have explained the mild symptoms in the patient with the 2810delT mutation. We also discovered that treating liver cancer cells with a Na+/H+ exchanger inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride, significantly enhanced the expression of the alternative splice variant of ATP7B lacking exon 12. Conclusion: This study suggests a novel therapeutic strategy for patients with mutations in exon 12. (Hepatology 2010;52:1662-1670)
關聯:	HEPATOLOGY
显示于类别:	[生物科技學系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
		0Kb	Unknown	232	检视/开启
index.html		0Kb	HTML	505	检视/开启

在ASIAIR中所有的数据项都受到原著作权保护.

数据加载中.....