The molecular basis of alkaptonuria
The molecular basis of alkaptonuria
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DOI：
10.1038/ng0996-19
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发表时间：
1996-09-01
期刊：
影响因子：
30.8
通讯作者：
deCordoba, SR
中科院分区：
文献类型：
--
作者：
FernandezCanon, JM;Granadino, B;deCordoba, SR
白蛋白尿症（AKU）在人类遗传学史上占有独特的地位，因为它是Garrod在1902年解释为孟德尔隐性性状的第一种疾病。尿黑酸是一种罕见的代谢性疾病，由尿黑酸1，2双加氧酶（HGO）活性丧失引起。受影响的个人积累大量的尿黑酸，酪氨酸和苯丙氨酸的catalysis的中间产物，使尿液变暗并沉积在结缔组织中，引起衰弱性关节炎。本文报道了人HGO基因的克隆，并确定其为AKU基因。我们表明，HGO映射到相同的位置描述为AKU，说明HGO窝藏与疾病共分离的错义突变，并提供生化证据表明，这些错义突变中至少有一个是功能丧失突变。
Alkaptonuria (AKU) occupies a unique place in the history of human genetics because it was the first disease to be interpreted as a mendelian recessive trait by Garrod in 1902. Alkaptonuria is a rare metabolic disorder resulting from loss of homogentisate 1,2 dioxygenase (HGO) activity. Affected individuals accumulate large quantities of homogentisic acid, an intermediary product of the catabolism of tyrosine and phenylalanine, which darkens the urine and deposits in connective tissues causing a debilitating arthritis. Here we report the cloning of the human HGO gene and establish that it is the AKU gene. We show that HGO maps to the same location described for AKU, illustrate that HGO harbours missense mutations that cosegregate with the disease, and provide biochemical evidence that at least one of these missense mutations is a loss-of-function mutation.