The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA
The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA
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DOI：
10.1111/j.1365-2141.2006.06143.x
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发表时间：
2006-07-01
影响因子：
6.5
通讯作者：
Beutler, Ernest
中科院分区：
文献类型：
--
作者：
Flanagan, Jonathan M.;Rhodes, Melissa;Beutler, Ernest
磷酸甘油酸激酶(PGK)缺乏是一种罕见的X连锁疾病，其特征是轻度至严重的溶血性贫血、横纹肌溶解和中枢神经系统的各种缺陷。在一个美国白人家庭中，两个儿子出现溶血性贫血、癫痫发作和发育迟缓。PGK缺乏症的诊断是基于极低的红细胞PGK酶活性水平(相当于正常水平的5%)和一个错义(c.491a->；T)PGK1基因突变。这种突变导致了Asp164Val氨基酸替换，以前被命名为PGK-Amiens和PGK-New York。这两名新患者具有完整的PGK缺乏临床综合征，包括溶血性贫血、发育迟缓和癫痫，先证者有偏瘫偏头痛、视网膜营养不良和肌肉疲劳。PGK-Amiens/New York突变此前曾在一个法国患者和一个华裔澳大利亚大家庭中被发现，这表明要么c.91a->；T突变是一种反复突变，要么是迄今为止已被确认为该突变的患者之间存在共同的祖先。对c.91a->；T突变的单倍型分析表明，这是一种反复发生的突变。
Phosphoglycerate kinase (PGK) deficiency is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system. In a white American family, two sons presented with haemolytic anaemia, seizures, and developmental delay. The diagnosis of PGK deficiency was made based on the remarkably low (< 5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A -> T) PGK1 gene mutation. This mutation results in an Asp164Val amino acid substitution, which has previously been designated PGK-Amiens and PGK-New York. The two new patients have the full clinical syndrome of PGK deficiency including haemolytic anaemia, developmental delay and seizures, and in the proband, hemiplegic migraines, retinal dystrophy and muscle fatigue. The PGK-Amiens/New York mutation had previously been found in a French patient and also in a large Chinese-Australian kindred, indicating that either the c. 91A -> T mutation is a recurrent mutation or that there is shared ancestry between the patients that have been identified so far with the mutation. Haplotype analysis of the c. 91A -> T mutation indicated that this was a recurrent mutation.