Tamary Hannah, Dgany Orly, Proust Alexis, Krasnov Tatyana, Avidan Nili, Eidelitz-Markus Tal, Tchernia Gil, Geneviève David, Cormier-Daire Valérie, Bader-Meunier Brigitte, Ferrero-Vacher Corinne, Munzer Martine, Gruppo Ralph, Fibach Eithan, Konen Osnat, Yaniv Isaac, Delaunay Jean
Paediatric Haematology Laboratory, Felsenstein Medical Research Centre, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Br J Haematol. 2005 Aug;130(4):628-34. doi: 10.1111/j.1365-2141.2005.05642.x.
Congenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone disease has only occasionally been associated with this disease. CDA I is caused by mutations in the CDAN1 gene encoding for codanin-1. Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease. Six novel mutations in the CDAN1 gene were identified. In two patients, one mutation and in another, both mutations were elusive. No patient was homozygous for a null-type mutation. However, one patient with complex bone disease was homozygous for a splice-site mutation (IVS-12+5G>A). Western blotting revealed that codanin-1 synthesis was 65% less than the control. Five single nucleotide polymorphisms (SNPs) previously unreported in the literature or the SNP database were also identified. Although the absence of codanin-1 is probably lethal, the presence of 35% of the protein was compatible with life but was associated with severe clinical manifestations. However, in most patients studied, no correlation could be established between the expected levels of codanin-1 or the nature of the mutation and the severity of the clinical manifestations.
I型先天性红细胞生成异常性贫血（CDA）是一种罕见的遗传性疾病，其特征为红细胞生成无效和大细胞性贫血。复杂的骨骼疾病仅偶尔与该病相关。CDA I由编码科达宁-1的CDAN1基因突变引起。我们的目的是对8例散发性CDA I的非亲缘患者中的CDAN1突变进行特征分析，其中3例患有复杂的骨骼疾病。在CDAN1基因中鉴定出6种新突变。在2例患者中发现了1种突变，在另1例患者中发现了2种突变，但有1种突变难以捉摸。没有患者为无效型突变的纯合子。然而，1例患有复杂骨骼疾病的患者为剪接位点突变（IVS-12+5G>A）的纯合子。蛋白质印迹分析显示，科达宁-1的合成比对照少65%。还鉴定出5种先前在文献或SNP数据库中未报道的单核苷酸多态性（SNP）。虽然缺乏科达宁-1可能是致命的，但35%的该蛋白质的存在与生命相容，但与严重的临床表现相关。然而，在大多数研究的患者中，无法在预期的科达宁-1水平或突变性质与临床表现的严重程度之间建立相关性。
