Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X
Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X
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分子遗传学分析诊断日本HHH综合征患者：常见突变R179X
DOI：
10.1007/s100380170075
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发表时间：
2001
影响因子：
3.5
通讯作者：
S. Tsujino
中科院分区：
文献类型：
--
作者：
T. Miyamoto;N. Kanazawa;Shigeo Kato;M. Kawakami;Y. Inoue;T. Kuhara;Takehiko Inoue;K. Takeshita;S. Tsujino
摘要线粒体鸟氨酸转运蛋白缺乏症（或HHH综合征）患者表现出多种神经系统症状，包括智力迟钝、痉挛性截瘫伴锥体征、小脑性共济失调、高氨血症引起的间歇性意识障碍或昏迷。我们之前在日本HHH综合征患者中描述了ORNT1基因的三个新突变。在这篇文章中，我们报告了一名新的HHH综合征患者，一名52岁的女性，除了没有智力迟钝外，她具有典型的临床特征。当我们筛选该患者以及先前描述的日本患者的ORNT1基因突变时，我们发现两者都是无义突变（R179X）的纯合子。此外，来自一名患者的成纤维细胞RNA的逆转录(RT)-聚合酶链反应（PCR）显示外显子4跳变，这在先前报道的R179X患者中观察到。这些结果与我们之前报告的结果一起表明，在我们报告的5例日本HHH患者中有3例（10个等位基因中有6个）存在R179X，这表明这是日本HHH综合征患者中常见的突变。
AbstractPatients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.