ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy
ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy
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DOI：
10.1136/bjo.2003.021527
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发表时间：
2004-02-01
影响因子：
4.1
通讯作者：
Yasuda, T
中科院分区：
文献类型：
--
作者：
Jiang, Y;Matsuo, T;Yasuda, T
目的：检测先天性上斜肌麻痹患者ARiX基因的多态性，探讨ARiX基因与先天性上斜肌麻痹的关系。方法：对15例上斜肌麻痹患者(先天性13例，获得性瘫痪2例)和54例正常人的ARiX基因3个外显子进行基因组DNA扩增和直接测序。将扩增产物克隆到载体上，并进行测序。结果：4例先天性上斜肌麻痹患者携带ARiX基因杂合性核苷酸突变。1例上斜肌缺失患者外显子1的5‘端非编码区为T7C，启动子区域为C-44A，两者位于同一条链上。另1例先天性上斜肌麻痹患者外显子1的5‘非编码区C76G和启动子区域的C-9A位于同一链上。在一个先天性上斜肌麻痹家系中发现了外显子1 5‘-UTR5’-UTRG153A。外显子1 5‘端非编码区的G153A也存在于4名无关的正常人中。结论：1个先天性上斜肌麻痹家系共分离有外显子1 5‘-UTR5’-UTR区的G153A核苷酸改变。仅在先天性上斜肌麻痹患者中发现了外显子1或启动子区域的其他四个核苷酸变化。这些核苷酸多态性可能是先天性上斜肌麻痹发生的危险因素之一。
Aim: To identify ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy and to find the relation between the ARIX gene and congenital superior oblique muscle palsy.Methods: The three exons of the ARIX gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 15 patients with superior oblique muscle palsy (13 with congenital and two with acquired palsy) and 54 normal individuals. PCR products cloned into plasmids were also sequenced. A family with father and a daughter each having congenital superior oblique muscle palsy was also involved in this study.Results: Four patients with congenital superior oblique muscle palsy carried heterozygous nucleotide changes in the ARIX gene. One patient with the absence of the superior oblique muscle had T7C in the 5'-UTR of the exon 1 and C-44A in the promoter region, both of which were located on the same strand. Another unrelated patient with congenital superior oblique muscle palsy had C76G in the 5'-UTR of the exon 1 and C-9A in the promoter region on the same strand. G153A in the 5'-UTR of exon 1 was found in common in two affected members of a family with congenital superior oblique muscle palsy. This G153A in the 5'-UTR of exon 1 was also present in four unrelated normal individuals. No other heterozygous nucleotide changes were found in normal individuals.Conclusions: The nucleotide change (G153A) in the 5'-UTR of exon 1 co-segregated with congenital superior oblique muscle palsy in one family. Four other nucleotide changes in the exon 1 or the promoter region were found only in patients with congenital superior oblique muscle palsy. These nucleotide polymorphisms may be one of the risk factors for the development of congenital superior oblique muscle palsy.