Edgar A J, Wickramasinghe S N
Department of Haematology, Imperial College School of Medicine, St Mary's Hospital, London.
Br J Haematol. 1998 Feb;100(2):389-92. doi: 10.1046/j.1365-2141.1998.00569.x.
DNA sequencing of the coding region of the erythroid 5-aminolaevulinate synthase (ALAS2) cDNA from a male with pyridoxine-responsive sideroblastic anaemia revealed a missense mutation C1622G and a closely linked polymorphism C1612A in exon 10 of the gene. Sequence analysis of the genomic DNA from other family members revealed that the proband's mother and daughter were heterozygous carriers of the mutation, consistent with the X-linked inheritance. The C1622G mutation results in a histidine to aspartic acid substitution at amino acid residue 524. The histidine residue is conserved in both the erythroid and housekeeping ALAS proteins in vertebrates, all other known ALAS proteins and other oxamine synthases that have pyridoxal 5'-phosphate as a co-factor. This histidine is located in a predicted loop, preceding a long alpha-helix region near the carboxy-terminus.
对一名患有吡哆醇反应性铁粒幼细胞贫血的男性患者的红系5-氨基乙酰丙酸合酶（ALAS2）cDNA编码区进行DNA测序，结果显示在该基因第10外显子中有一个错义突变C1622G和一个紧密连锁的多态性C1612A。对其他家庭成员的基因组DNA进行序列分析发现，先证者的母亲和女儿是该突变的杂合携带者，这与X连锁遗传一致。C1622G突变导致氨基酸残基524处的组氨酸被天冬氨酸取代。在脊椎动物的红系和管家ALAS蛋白、所有其他已知的ALAS蛋白以及其他以磷酸吡哆醛为辅因子的氨基氧化酶中，组氨酸残基都是保守的。该组氨酸位于一个预测的环中，在靠近羧基末端的一个长α螺旋区域之前。
