铁粒幼细胞贫血家系一个新的ALAS2基因突变  

A novel mutation of the ALAS2 gene in a family with X linked sideroblastic anemia

作　　者：朱平[1] 卜定方[1] 

机构地区：[1]北京医科大学第一医院,100034

出　　处：《中华血液学杂志》2000年第9期478-481,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目!(3957321);卫生部科研基金资助项目!(982 2220)

摘　　要：目的　确定一个铁粒幼细胞贫血家系是由于ALAS2基因突变所致。方法　用聚合酶链反应扩增X染色体上与ALAS2距离小于 1.7Mb的微卫星DXS 991和DXS 1199,用变性凝胶电泳进行 3代家族成员 9人 (包括第 2代 2例患者 )的单体型分析 ;克隆患者以及正常人ALAS2基因的cDNA全部编码区 ,并测序比较。结果　该家系 2例先证者都从母亲获得同一ALAS2等位基因。健康兄、妹 2人则获得另一条ALAS2等位基因。克隆患者和正常人ALAS2cDNA编码区后测序发现 ,患者第 5外显子A5 2 3G突变 ,导致苏氨酸变为丙氨酸 ;第 3外显子T372C突变 ,导致亮氨酸由脯氨酸替代 ,后者在ALAS2可剪拼区内 ,意义尚不明确。结论　在X连锁遗传性铁粒幼细胞贫血家系新发现了一种导致发病的ALAS2基因第Objective To confirm the mutation of ALAS2 gene is the cause of sideroblastic anemia in a family. Methods Polymerase chain reaction (PCR) was used to amplify the microsatellite DXS 991, DXS 1199 in the chromosome Xp11.22 linked gene ALAS2 and haplotype analysis was performed in a kindred with 2 patients and 7 normal members. All cDNA encoded regions in the ALAS2 gene of the patients and their normal siblings were cloned, sequenced and compared. Result Both brother patients had the same allele of ALAS2 and their normal siblings did not. The mutation in the patients’ ALAS2 gene was exon 5 A523G, causing threonine to alanine; and exon 3 T372C, leucine to proline. The latter located in the splicing region, its significance is not clear. Conclusion The pathogenesis of this kindred of X linked sideroblastic anemia (XLSA) involved a novel mutation in ALAS2 exon 5.

关 键 词：铁粒幼细胞贫血 家系 ALAS2 基因突变 PCR 

分 类 号：R556[医药卫生—血液循环系统疾病]