摘要

Low copper and ceruloplasmin in serum are the diagnostic hallmarks for Menkes disease, Wilson disease, and aceruloplasminemia. We report on five patients from four unrelated families with these biochemical findings who presented with a lethal autosomal-recessive syndrome of congenital cataracts, hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous or compound heterozygous mutations for all affected subjects in SLC33A1 encoding a highly conserved acetylCoA transporter (AT-1) required for acetylation of multiple gangliosides and glycoproteins. The mutations were found to cause reduced or absent AT-1 expression and abnormal intracellular localization of the protein. We also showed that AT-1 knockdown in HepG2 cells leads to reduced ceruloplasmin secretion, indicating that the low copper in serum is due to reduced ceruloplasmin levels and is not a sign of copper deficiency. The severity of the phenotype implies an essential role of AT-1 in proper posttranslational modification of numerous proteins, without which normal lens and brain development is interrupted. Furthermore, AT-1 defects are a new and important differential diagnosis in patients with low copper and ceruloplasmin in serum.

译文

血清中的低铜和铜蓝蛋白是 Menkes 病、 Wilson 病和无浆纤溶血症的诊断标志。我们报告了来自四个不相关家族的五名患者,他们的生化结果显示患有致命的常染色体隐性遗传综合征先天性白内障、听力损失和严重的发育迟缓。脑部 MRI 显示明显的小脑发育不全和肌萎缩。进行纯合性定位,并在染色体 3q25 处显示三个家系之间的共性区域。深度测序和常规测序揭示了 SLC33A1 中所有受累受试者的纯合或复合杂合突变,编码多种神经节苷脂和糖蛋白乙酰化所需的高度保守的乙酰 coa 转运蛋白 (AT-1)。发现这些突变会导致 AT-1 表达减少或缺失以及蛋白质的异常细胞内定位。我们还表明,在肝癌细胞中 AT-1 击倒会导致铜蓝蛋白分泌减少,这表明血清中的低铜是由于铜蓝蛋白水平降低造成的,而不是铜缺乏的迹象。表型的严重性意味着 AT-1 在大量蛋白质的适当翻译后修饰中的重要作用,没有它,正常的晶体和大脑发育就会中断。此外,AT-1 缺陷是血清中低铜和铜蓝蛋白患者的一种新的重要鉴别诊断。

ceruloplasmin

消化 消化疾病鉴别指标 临床研究术语
概述  :  

铜氧化酶(ceruloplasmin,CP)又称铜蓝蛋白,是一种含铜具有氧化酶的α2-球蛋白,相对分子质量为151×103,每个分子含8个铜原子,含铜量为0.34%,血清中约95%的铜与α2-球蛋白结合成铜蓝蛋白,起调节铁吸收和运输作用,具有亚铁氧化酶及胺氯化酶活性,在人体中铜蓝蛋白的正常含量250-430U/ml,无年龄、性别差异。CP作为一个急性期的反应蛋白,在许多病理情况下可升高,如肿瘤、感染等;在一些生理状况下,如妊娠、口服避孕药等也可升高。CP为球蛋白,它

Ceruloplasmin 英/sɪ,ruːləʊ'plæzmɪn/  美 /sə,rʊlo'plæzmɪn/

释义   n.血浆铜蓝蛋白

例句   To investigate the diagnostic value of serum copper and non-ceruloplasmin-bound copper determination in patients with Wilson disease (WD).  探讨血清铜和血清游离铜对肝豆状核变性的诊断价值。


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