Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13).
Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13).
复制标题
ABCB7 基因缺失：难治性贫血伴等双着丝粒环状铁粒幼细胞 (X)(q13) 中成红细胞线粒体铁积累的发病机制。
DOI：
10.1007/s12185-011-0786-y
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发表时间：
2011
期刊：
影响因子：
2.1
通讯作者：
Kohgo Y.
中科院分区：
文献类型：
--
作者：
Sato K;Torimoto Y;Hosoki T;Ikuta K;Takahashi H;Yamamoto M;Ito S;Okamura N;Ichiki K;Tanaka H;Shindo M;Hirai K;Mizukami Y;Otake T;Fujiya M;Sasaki K;Kohgo Y.
等双着丝粒 (X)(q13) (idicXq13) 是一种罕见的获得性染色体异常，起源于 Xq13 (Xq13-qter) 长臂的缺失，常见于患有涉及环状铁粒幼细胞 (RS) 增加的血液学疾病的女性患者，其特征是红细胞核周围线粒体铁积聚。 idicXq13 患者 RS 增加的原因尚不完全清楚。在这里，我们报告了一名 66 岁女性的病例，该患者患有难治性贫血，伴有环状铁粒幼细胞 (RARS)，G 带分析显示 idicXq13。通过荧光原位杂交 (FISH) 分析和患者骨髓细胞中 ABCB7 mRNA 表达水平的降低，我们确定了位于 Xq13 上并参与线粒体铁向细胞质转运的 ABCB7（ATP 结合盒亚家族 B 成员 7）基因的丢失。进一步的 FISH 分析表明，ABCB7 基因仅在活性 X 染色体上丢失，而在非活性 X 染色体上则没有。我们认为，由于 idicXq13 形成时 Xq13-qter 的缺失，ABCB7 的丢失可能导致该患者 RS 增加。这些发现表明ABCB7基因的缺失可能是具有idicXq13的RARS患者线粒体铁积累的致病因素。
An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of theABCB7(ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level ofABCB7mRNA in the patient’s bone marrow cells. Further FISH analyses showed that theABCB7gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss ofABCB7due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of theABCB7gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.