E109K Is a SEC23B Founder Mutation among Israeli Moroccan Jewish Patients with Congenital Dyserythropoietic Anemia Type II
E109K Is a SEC23B Founder Mutation among Israeli Moroccan Jewish Patients with Congenital Dyserythropoietic Anemia Type II
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DOI：
10.1159/000322948
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发表时间：
2011-01-01
影响因子：
2.4
通讯作者：
Tamary, Hannah
中科院分区：
文献类型：
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作者：
Amir, Achiya;Dgany, Orly;Tamary, Hannah
目的：先天性红细胞生成异常性贫血（CDA）是以红细胞生成障碍、红系前体细胞双核和继发性血色素沉着为特征的疾病。最近，在CDA II型（CDA II）中突变的基因SEC 23 B被鉴定。所有患有CDA II的以色列患者都是北非（主要是摩洛哥）犹太血统。我们研究了这些患者中CDA II的分子基础。方法：研究对象包括11例CDA II患者，来自8个明显无关的家庭。从医疗档案中检索临床数据，并收集血液进行DNA分析。结果：大多数患者（10/11）是一个常见的SEC 23 B突变（E109 K）的纯合子。单倍型分析显示所有患者具有共同的遗传背景。1例患者为E109 K突变和新突变T710 M的复合杂合子。所有患者均不依赖输血，随着年龄的增长，铁超载增加。我们估计E109 K突变有2,400年的历史，与犹太人的移民历史一致。结论：以色列的大多数CDA II患者是摩洛哥犹太人，携带一种常见的SEC 23 B突变E109 K，这是第一个被描述为导致CDA II的创始人突变。如前所述，携带2个错义突变与相对不严重的表型相关。版权所有（C）2011 S. Karger AG，巴塞尔
Objective: Congenital dyserythropoietic anemia (CDA) is characterized by ineffective erythropoiesis, binuclearity of erythroid precursors and secondary hemochromatosis. Recently, the gene mutated in CDA type II (CDA II), SEC23B, was identified. All Israeli patients with CDA II are of North African (mainly Moroccan) Jewish descent. We investigated the molecular basis of CDA II in those patients. Methods: Participants included 11 patients with CDA II from 8 apparently unrelated families. Clinical data were retrieved from medical files, and blood was collected for DNA analysis. Results: The majority of patients (10/11) were homozygous for a common SEC23B mutation (E109K). Haplotype analysis revealed a common genetic background in all patients. One patient was a compound heterozygote for the E109K mutation and a novel mutation, T710M. All patients were transfusion independent, with increasing iron overload with age. We estimate the E109K mutation to be 2,400 years old, in line with Jewish migration history. Conclusions: Most CDA II patients in Israel are of Moroccan Jewish origin and carry a common SEC23B mutation, E109K, the first to be described as a founder mutation causing CDA II. As previously suggested, carrying 2 missense mutations is associated with a relatively non-severe phenotype. Copyright (C) 2011 S. Karger AG, Basel