Department of Molecular Medicine and Medical Biotechnologies, University Federico II of Naples, Naples, Italy.
Blood Cells Mol Dis. 2013 Jun;51(1):17-21. doi: 10.1016/j.bcmd.2013.02.003. Epub 2013 Mar 1.
Congenital dyserythropoietic anemia type II, a recessive disorder of erythroid differentiation, is due to mutations in SEC23B, a component of the core trafficking machinery COPII. In no case homozygosity or compound heterozygosity for nonsense mutation(s) was found. This study represents the first description of molecular mechanisms underlying SEC23B hypomorphic genotypes by the analysis of five novel mutations. Our findings suggest that reduction of SEC23B gene expression is not associated with CDA II severe clinical presentation; conversely, the combination of a hypomorphic allele with one functionally altered results in more severe phenotypes. We propose a mechanism of compensation SEC23A-mediated which justifies these observations.
先天性红细胞生成性血卟啉病 II 型是一种常染色体隐性红细胞分化紊乱，由 COPII 核心运输机制的组成部分 SEC23B 的突变引起。在任何情况下均未发现无义突变（s）的纯合子或复合杂合子。这项研究通过分析五个新突变，首次描述了 SEC23B 低功能基因型的分子机制。我们的研究结果表明，SEC23B 基因表达的减少与 CDA II 严重临床表现无关；相反，低功能等位基因与一个功能改变的等位基因的组合导致更严重的表型。我们提出了一种由 SEC23A 介导的代偿机制，可以解释这些观察结果。
