Two new severe mutations causing guanidinoacetate methyltransferase deficiency.
Two new severe mutations causing guanidinoacetate methyltransferase deficiency.
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两种新的严重突变导致胍基乙酸甲基转移酶缺乏。
DOI：
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发表时间：
2000
影响因子：
3.8
通讯作者：
I. Antonozzi
中科院分区：
文献类型：
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作者：
C. Carducci;V. Leuzzi;C. Carducci;S. Prudente;L. Mercuri;I. Antonozzi
肌酸代谢的原发性疾病直到最近才被描述。我们报告了从一名患有胍基乙酸甲基转移酶缺陷的儿童身上获得的新的分子和生化发现。该患者在出生第一年出现神经退行、癫痫和运动障碍。 HPLC 分析显示尿液、血浆和脑脊液中含有高浓度的胍基乙酸。 cDNA 和基因组 DNA 的分子分析揭示了两个新突变，即外显子 5 中 cDNA (c.491insG) 核苷酸 491 后的 G 插入和内含子 5 中 nt -3 处的颠换 (IVS5-3C>G)。 c.491insG 突变会导致外显子末端发生移码和过早终止密码子。 IVS5-3C>G 突变阻止基因最后一个外显子的剪接，从而阻碍转录物的完全成熟，并且很可能导致 mRNA 的快速降解。
Primary disorders of creatine metabolism have been only recently described. We report new molecular and biochemical findings obtained from a child affected by guanidinoacetate methyltransferase deficiency. This patient presented with neurological regression, epilepsy, and a movement disorder during the first year of life. HPLC analysis showed high concentrations of guanidinoacetic acid in urine, plasma, and CSF. Molecular analyses of cDNA and genomic DNA revealed two novel mutations, a G insertion following nucleotide 491 of the cDNA (c.491insG) in exon 5 and a transversion at nt -3 in intron 5 (IVS5-3C>G). The c.491insG mutation causes a frameshift and a premature stop codon at the end of the exon. The IVS5-3C>G mutation prevents the splicing of the last exon of the gene precluding the complete maturation of the transcript and, most likely, causes rapid degradation of the mRNA.
RNA 剪接缺陷和翻译阅读框缩短的后果。
影响因子：
9.8
作者：
Maquat,LE
通讯作者：
Maquat,LE