Hirano M, Tamaru Y, Nagai Y, Ito H, Imai T, Ueno S
Department of Medical Genetics, Nara Medical University, Japan.
Biochem Biophys Res Commun. 1995 Aug 15;213(2):645-51. doi: 10.1006/bbrc.1995.2180.
We report a novel mutation at a splice site in the GTP cyclohydrolase I gene in a Japanese family with hereditary progressive dystonia with marked diurnal fluctuation (HPD)/dopa responsive dystonia (DRD). Reverse transcriptase-initiated PCR (RT-PCR) of lymphocyte mRNA showed both normal and small size fragments in the HPD patient and his asymptomatic mother. Sequence analysis revealed that skip splicing of exon 1 to exon 3 occurred in the small fragment. The patient and his mother were heterozygous for G --> C substitution at conserved consensus sequence GT at 5' end of the intron 2. Quantitative RT-PCR showed that the expression of normal GTP cyclohydrolase I mRNA decreased in their lymphocytes, while the HPD patient had more expression of mutant GTP cyclohydrolase I mRNA than his asymptomatic mother.
我们报告了一个日本家族中，患有遗传性进行性肌张力障碍伴显著日波动（HPD）/多巴反应性肌张力障碍（DRD）的家系，其GTP环化水解酶I基因的剪接位点存在一种新的突变。对淋巴细胞mRNA进行逆转录酶引发的PCR（RT-PCR）分析显示，该HPD患者及其无症状母亲的样本中既有正常大小的片段，也有小片段。序列分析表明，小片段中发生了外显子1到外显子3的跳跃剪接。患者及其母亲在内含子2 5'端保守共有序列GT处存在G→C替换的杂合突变。定量RT-PCR显示，他们淋巴细胞中正常GTP环化水解酶I mRNA的表达减少，而HPD患者突变型GTP环化水解酶I mRNA的表达比其无症状母亲更多。
