Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1
Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1
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DOI：
10.1038/6831
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发表时间：
1999-03-01
期刊：
影响因子：
30.8
通讯作者：
Krahe, R
中科院分区：
文献类型：
--
作者：
Aminoff, M;Carter, JE;Krahe, R
巨幼细胞性贫血1（MGA 1，OMIM 261100）是一种罕见的常染色体隐性遗传疾病，其特征为幼年巨幼细胞性贫血，以及可能是唯一表现的神经系统症状（1，2）。在细胞水平，MGA 1的特征在于选择性肠维生素B-12（B-12，钴胺素）吸收不良-2。MGA 1在世界范围内发生，但其患病率在几个中东国家（3-6）和挪威（1，7）较高，芬兰最高（0.8/100，000）。我们先前通过芬兰和挪威家系的连锁分析将MGA 1基因定位于染色体10p12.1上的一个6 cM区域（参考文献8）。最近克隆了编码内因子（IF）-B-12受体cubilin的功能性候选基因（9，10）;人类同源物CUBN定位于同一区域（10）。我们现在已经完善了MGA 1区域的连锁不平衡（LD）映射，精细映射CUBN和确定两个独立的疾病特异性CUBN突变在17个芬兰MGA 1家族。我们的遗传和分子数据表明，CUBN突变导致MGA 1。
Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic: anaemia, as well as neurological symptoms that may be the only manifestations(1,2). At the cellular level, MGA1 is characterized by selective intestinal vitamin B-12 (B-12, cobalamin) malabsorption-2. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries(3-6) and Norway(1,7), and highest in Finlands (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B-12 receptor, cubilin, was recently cloned(9,10); the human homologue, CUBN, was mapped to the same region(10). We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.