铁粒幼细胞贫血家系一个新的ALAS2基因突变

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ＤＸＳ９９１和ＤＸＳ１１９９，用变性凝胶电泳进行了３代家族成员９个（包括第２代２例患）的单体型分析；克隆患以及正常人ＡＬＡＳ２基因的ｃＤＮＡ全部编码区，并测序比较。结果该家系２例先证都从母亲获得同一ＡＬＡＳ２等位基因。健康史、妹２人编码区，并测序比较。结果该家系

A novelmutation of the ALAS2 gene in a family with X-linked sideroblastic anemia

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.