Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease.
Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease.
复制标题
铜蓝蛋白基因无义突变导致糖尿病和神经退行性疾病的特征。
DOI：
10.1093/hmg/5.1.81
复制
发表时间：
1996
影响因子：
3.5
通讯作者：
Gitlin,JD
中科院分区：
文献类型：
--
作者：
Takahashi,Y;Miyajima,H;Shirabe,S;Nagataki,S;Suenaga,A;Gitlin,JD
我们在此报告一位患有胰岛素依赖性糖尿病的 45 岁女性的铜蓝蛋白基因突变的特征，该女性最近出现步态障碍和构音障碍。体格检查显示步态共济失调、扫描言语和视网膜变性。大脑的磁共振成像与基底神经节铁含量增加一致，实验室研究显示血清铁浓度较低，并且未检测到血清铜蓝蛋白。该患者铜蓝蛋白基因的核苷酸序列分析显示，外显子 15 中存在 G 至 A 取代，导致氨基酸 858 (Trp858ter) 处发生无义突变。该患者的弟弟、无神经症状的弟弟也被发现是这种突变的纯合子。临床和遗传数据综合起来支持铜蓝蛋白在人类铁代谢中重要且独特的作用的概念。这一家族的鉴定扩展了导致这种常染色体隐性迟发性神经退行性疾病的铜蓝蛋白基因突变谱，并强调了认识到铜蓝蛋白血症作为糖尿病和神经系统疾病的遗传原因的重要性。
We report here on the characterization of a mutation in the ceruloplasmin gene in a 45 year old woman with insulin-dependent diabetes mellitus who presented with the recent onset of gait disturbance and dysarthria. Physical examination revealed an ataxic gait, scanning speech and retinal degeneration. Magnetic resonance imaging of the brain was consistent with increased basal ganglia iron content and laboratory studies revealed a low serum iron concentration and no detectable serum ceruloplasmin. Nucleotide sequence analysis of the ceruloplasmin gene from this patient revealed a G to A substitution in exon 15 resulting in a nonsense mutation at amino acid 858 (Trp858ter). The patient's younger, neurologically asymptomatic brother was also found to be homozygous for this mutation. Taken together the clinical and genetic data support the concept of an essential and unique role for ceruloplasmin in human iron metabolism. Identification of this kindred extends the spectrum of ceruloplasmin gene mutations resulting in this autosomal recessive, late-onset neurodegenerative disease and highlights the importance of recognizing aceruloplasminemia as a genetic cause of diabetes and neurologic disease.