Nonsense mutation of feline β-hexosaminidase β-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats
Nonsense mutation of feline β-hexosaminidase β-subunit (HEXB) gene causing Sandhoff disease in a family of Japanese domestic cats
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DOI：
10.1016/j.rvsc.2006.05.007
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发表时间：
2007-02-01
影响因子：
2.4
通讯作者：
Hayashi, M.
中科院分区：
文献类型：
--
作者：
Kanae, Y.;Endoh, D.;Hayashi, M.
G（M2）神经节苷脂沉积症是一种遗传性代谢疾病，由溶酶体P-己糖胺酶的酶活性严重降低引起。在本研究中，开放阅读框（ORF）的HEXB基因在日本家猫与G（M2）神经节苷脂沉积症变异0（山德霍夫病）的家庭进行了测定。两种类型的异常cDNA克隆，从受影响的猫组织的肝脏中获得。其中一个在HEXB ORF的核苷酸位置667处显示从C到T的单核苷酸取代。在推导的氨基酸序列中，精氨酸密码子被改变为终止密码子。采用PCR引物引入限制性内切酶分析进行基因分型，证实该家系的Sandhoff病与该无义突变有关。无义突变的发现将允许结合已经建立的基于酶的测试来确认Sandhoff病的临床诊断。(c)2006爱思唯尔有限公司保留所有权利。
G(M2) gangliosidoses are inherited metabolic disorders and are caused by severely reduced enzymatic activity of lysosomal P-hexosaminidase. In the present study, the open reading frame (ORF) of the HEXB gene in a family of Japanese domestic cats with G(M2) gangliosidosis variant 0 (Sandhoff disease) was determined. Two types of abnormal cDNA clones were obtained from the liver of an affected cat tissue. One showed a single nucleotide substitution from C to T at nucleotide position 667 of the HEXB ORF. In the deduced amino acid sequence, the codon of arginine was altered to a stop codon. The genotyping, using PCR-primer introduced restriction analysis confirmed that Sandhoff disease in this family is associated with this nonsense mutation. Discovery of the nonsense mutation will permit the confirmation of the clinical diagnosis of Sandhoff disease in conjugation with the already established enzyme-based test. (c) 2006 Elsevier Ltd. All rights reserved.