Fernández-Cañón J M, Granadino B, Beltrán-Valero de Bernabé D, Renedo M, Fernández-Ruiz E, Peñalva M A, Rodríguez de Córdoba S
Departmento de Microbiologia Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Nat Genet. 1996 Sep;14(1):19-24. doi: 10.1038/ng0996-19.
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.
黑尿症（AKU）在人类遗传学史上占据着独特的地位，因为它是1902年被加罗德解释为孟德尔隐性性状的第一种疾病。黑尿症是一种罕见的代谢紊乱疾病，由尿黑酸1,2双加氧酶（HGO）活性丧失所致。患病个体积累大量尿黑酸，这是酪氨酸和苯丙氨酸分解代谢的中间产物，会使尿液变黑并沉积在结缔组织中，导致使人衰弱的关节炎。在此，我们报告人类HGO基因的克隆，并确定它就是AKU基因。我们表明HGO定位于与AKU所描述的相同位置，说明HGO存在与该疾病共分离的错义突变，并提供生化证据证明这些错义突变中至少有一个是功能丧失突变。
