Minchiotti Lorenzo, Galliano Monica, Caridi Gianluca, Kragh-Hansen Ulrich, Peters Theodore
Department of Molecular Medicine, University of Pavia, I-27100 Pavia, Italy.
Biochim Biophys Acta. 2013 Dec;1830(12):5494-502. doi: 10.1016/j.bbagen.2013.04.019. Epub 2013 Apr 21.
DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA).
To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA.
CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases.
Study of the defects in the ALB resulting in CAA allows the identification of "hot spot" regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.
对人白蛋白基因（ALB）编码区及其内含子/外显子连接区的DNA和mRNA测序已揭示出21种不同的分子缺陷，这些缺陷可导致先天性无白蛋白血症（CAA）。
从分子层面描述这些突变，并介绍目前关于CAA最重要的生化和临床影响的知识。
CAA较为罕见，但在特定的、遗传混合程度最低的人群中其发病率似乎明显更高。该病症尤其会影响脂质代谢，不过除了动脉粥样硬化并发症的风险可能增加外，在成年人中通常与轻微的临床症状相关。相比之下，几份报告表明，无白蛋白血症个体在围产期和儿童期可能处于危险之中，在此期间他们的发病率和死亡率似乎有所增加。这21种致病缺陷包括7个无义突变、7个影响剪接的变化、5个移码/缺失、1个移码/插入以及1个起始密码子突变。这些结果表明，该性状是一种等位基因异质性疾病，由缺陷的纯合（19例）或复合杂合（1例）遗传引起。大多数突变是独特的，但有一种名为开塞利（Kayseri）的突变导致了约一半的已知病例。
对导致CAA的ALB缺陷进行研究，有助于识别“热点”区域，并有助于理解该性状背后的分子机制。此类研究还可以提供有关ALB调控不同方面的分子信息，并阐明参与该蛋白质合成的调控机制。本文是名为《血清白蛋白》的特刊的一部分。
