Historical Vignette: Hypophosphatasia: Molecular Diagnosis of Rathbun's Original Case
Historical Vignette: Hypophosphatasia: Molecular Diagnosis of Rathbun's Original Case
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历史小插曲：低磷酸酯酶症：拉斯本原始病例的分子诊断
DOI：
10.1359/jbmr.2001.16.9.1724
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发表时间：
2001
影响因子：
6.2
通讯作者：
M. Whyte
中科院分区：
文献类型：
--
作者：
S. Mumm;Jonathan Jones;P. Finnegan;M. Whyte
1948年，约翰·坎贝尔·拉斯本（John Campbell Rathbun）博士将这种疾病描述为“低磷酸症”，当时他报告了一名死于佝偻病和癫痫的婴儿的血液和几个组织中碱性磷酸酶（ALP）活性的低水平，这似乎反映了“一种新的发育异常”。目前认为，低磷酸症是一种先天性代谢错误，其特征是由TNSALP失活突变引起的ALP组织非特异性同工酶（TNSALP）活性不足。在这里，我们表明，在Rathbun的病例报告50多年后，对亲本DNA的分析表明，TNSALP中涉及两个错义突变（G340A和A881C）的复合杂合导致了Rathbun患者的死亡。
In 1948, Dr. John Campbell Rathbun characterized the disorder “hypophosphatasia” when he reported paradoxically low levels of alkaline phosphatase (ALP) activity in blood and in several tissues from an infant who died with rickets and epilepsy, which seemed to reflect “a new developmental anomaly.” Hypophosphatasia is now recognized to be an inborn error of metabolism featuring deficient activity of the tissue‐nonspecific isoenzyme of ALP (TNSALP) caused by deactivating mutations in TNSALP. Here, we show, more than 50 years after Rathbun's case report, that analysis of the parental DNA indicates compound heterozygosity involving two missense mutations (G340A and A881C) in TNSALP caused the death of Rathbun's patient.