Abstract：
We report a novel ALAS2 gene mutation c.1315A>G (p.Lys439Glu) identified in a family, which caused evidently different hematologic phenotypes. The proband was a 17-year-old man with severe microcytic hypochromic anemia, excessive ring sideroblasts in the bone marrow, and iron overload. A hemizygous ALAS2 mutation in exon 9, c.1315A>G (p.Lys439Glu), was identified through sequence analysis. We assume that this amino acid substitution affects the enzymatic activity of ALAS2 by affecting its interaction with the cofactor pyridoxal 5\'-phosphate, since the patient was responsive to pyridoxine treatment. This novel mutation likely accounts for variable hematologic phenotypes in the family of this patient: his 15-year-old hemizygous brother was asymptomatic, while his heterozygous mother was mildly anemic.
摘要：
我们报道了一个新的ALAS2基因突变c.1315A>G（p。Lys439Glu）在一个家族中鉴定，导致明显不同的血液学表型。先证者是一名17岁的男性，患有严重的小细胞低色素性贫血，骨髓中过多的环铁皮母细胞，铁过载。外显子9中的半合子ALAS2突变，c.1315A>G（p。Lys439Glu），通过序列分析鉴定。我们假设这种氨基酸取代通过影响ALAS2与辅因子吡哆醛5'-磷酸的相互作用来影响ALAS2的酶活性，因为患者对吡哆醇治疗有反应。这种新的突变可能解释了该患者家庭中不同的血液学表型：他15岁的半合子兄弟无症状，而他的杂合母亲轻度贫血.
