摘要
1例有症状性镰状红细胞病女婴,虽然经新生儿筛查诊断为镰状细胞杂合型,但仍然因轻度低氧血症而病情恶化。经β球蛋白基因DNA序列测定发现:其母亲的β球蛋白等位基因正常,而其父亲的等位基因序列中,既发生了意料之中的镰状细胞病杂合突变(βGlu6Val),又有一处基因控制区中性突变(βLeu68Phe)。经蛋白质水平检验发现,患儿的血红蛋白是一种双重突变株蛋白, 称之为“牙买加平原血红蛋白”,其与氧的亲和力严重降低。蛋白分子结构模型显示:当氧压接近环境氧分压时, 该异常血红蛋白的氧合结构失去稳定性,这就是患儿杂合子镰状细胞病的分子机制。
A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newbornscreen-ing diagnosis of sickle cell trait. DNA sequencing of the P globin gene revealed that her maternal β globin allele was normal. Her paternal allele had not only the expected sickle-trait mutation, βGlu6Val, but also a second, charge-neutral mutation, βLeu68Phe. Analysis of the patient's hemoglobin revealed that the double-mutant protein, which we called 'hemoglobin Jamaica Plain, had severely reduced oxygen affinity. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen.
