Mutations and Polymorphisms
AKU presents a remarkable allelic heterogeneity. More than 40 different AKU mutations have been identified in a total series of less than 100 unrelated patients from many different countries (Fernández-Cańón et al., 1996; Gehrig et al., 1997; Beltrán-Valero de Bernabé et al., 1998; Ramos et al., 1998; Higashino et al., 1998; Beltrán-Valero de Bernabé et al., 1999;Beltrán-Valero de Bernabé et al., 1999; Muller et al., 1999; Walter et al., 1999; Felbor et al., 1999;Porfirio et al., 2000; Zatkova et al., 2000; unpublished data). (Click FIGURE-mut or TABLE-mut to see a detailed description of HGO mutations). The most prevalent mutation in Europe (excluding the Slovak AKU patients) is M368V, which represents approximately 20% of the AKU chromosomes. Similarly, V300G and P230S, each represent approximately 5% of the European AKU chromosomes. Slovakia is a country with a notable incidence of alkaptonuria (1:19,000) (Srsen et al., 1978). As many as 10 different AKU mutations were characterized in this country (Müller et al., 1999; Zatkova et al., 2000). The most prevalent mutations in Slovakia are G152fs, G161R, G270R and P370fs.
In addition to the AKU mutations, nineteen polymorphisms have been encountered within the human HGO gene (Granadino et al. (1997);Beltrán-Valero de Bernabé et al. (1998); unpublished data). Three of them, HGO-1, HGO-2, HGO-3, are dinucleotide repearts and sixteen Single Nucleotide Polymorphisms (SNPs) (Click FIGURE-pol or TABLE-pol to see a detailed description of HGO polymorphisms).
Location of mutations and polymorphisms in the HGO
gene DNA sequence: