An update on molecular genetics of Alkaptonuria (AKU)
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Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria, ochronosis, and ochronotic arthritis. The defect is caused by mutations in the HGD gene, which maps to the human chromosome 3q21–q23. AKU shows a very low prevalence (1:100,000–250,000) in most ethnic groups, but there are countries such as Slovakia and the Dominican Republic in which the incidence of this disorder rises to as much as 1:19,000. In this work, we summarize the genetic aspects of AKU in general and the distribution of all known disease-causing mutations reported so far. We focus on special features of AKU in Slovakia, which is one of the countries with an increased incidence of this rare metabolic disorder.
KeywordsHomogentisic Acid Ochronosis Alkaptonuria Human Splice Finder Intersubunit Interaction
This work was supported by IMPG SAS and FNS UK Bratislava, Slovakia.
- Al-Sbou M, Mwafi N (2010) Nine cases of alkaptonuria in one family in southern Jordan. Rheumatol Int (in press)Google Scholar
- Beltrán-Valero de Bernabé D, Jimenez FJ, Aquaron R, Rodríguez de Córdoba S (1999a) Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO). Am J Hum Genet 64:1316–1322PubMedCrossRefGoogle Scholar
- Garrod AE (1908) Croonian lectures on inborn errors of metabolism, lecture II: alkaptonuria. Lancet 2:73–79Google Scholar
- La Du BN (1958) Alkaptonuria. In: Scriver CR, Beauder AL, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw Hill, New York, pp 1371–1386Google Scholar
- La Du BN, Zannoni VG, Laster L, Seegmiller JE (1958) The nature of the defect in tyrosine metabolism in alcaptonuria. J Biol Chem 230:251–260Google Scholar
- Oexle K, Engel K, Tinschert S, Haas D, Lee-Kirsch MA (2008) Three-generational alkaptonuria in a non-consanguineous family. J Inherit Metab Dis. doi: 10.1007/s10545-008-0994-7
- Ranganath L, Taylor AM, Shenkin A et al (2011) Identification of alkaptonuria in the general population: a United Kingdom experience describing the challenges, possible solutions and persistent barriers. J Inherit Metab Dis 34:723–730Google Scholar
- Uyguner O, Goicoechea de Jorge E, Cefle A et al (2003) Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations. J Inherit Metab Dis 26:17–23PubMedCrossRefGoogle Scholar
- Zatkova A, Sedlackova T, Radvansky J et al (2011) Identification of eleven novel homogentisate 1,2 dioxygenase (HGD) variants in alkaptonuria (AKU) patients and establishment of a novel LOVD based HGD mutation database. J Inherit Metab Dis (in press)Google Scholar