PMID- 10482952
OWN - NLM
STAT- MEDLINE
DCOM- 19991101
LR  - 20091119
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 6
DP  - 1999 Sep
TI  - Allelic heterogeneity of alkaptonuria in Central Europe.
PG  - 645-51
AB  - Defects of the homogentisate 1,2 dioxygenase (HGO; E.C. No. 1.13.11.5) have been 
      identified as the molecular cause of alkaptonuria in humans (AKU) and the aku
      mouse. Here, we report on the genetic basis of 30 AKU patients from Central
      Europe. In addition to five mutations described previously, we have detected five
      novel HGO mutations. Recombinant expression of mutated HGO enzymes in E. coli
      demonstrates the inactivating effect of three of these mutations. A genetic
      epidemiologic study in Slovakia, the country with the highest incidence of
      alkaptonuria, demonstrates that two recurrent mutations (c.183-1G > A and
      Glyl61Arg) are found on more than 50% of AKU chromosomes. An analysis of the
      allelic association with intragenic DNA markers and of the geographic origins of 
      the AKU chromosomes suggests that several independent founders have contributed
      to the gene pool, and that subsequent genetic isolation is likely to be
      responsible for the high prevalence of alkaptonuria in Slovakia.
FAU - Muller, C R
AU  - Muller CR
AD  - Department of Human Genetics, University of Wurzburg, Biozentrum, Germany.
      crm@biozentrum.uni-wuerzburg.de
FAU - Fregin, A
AU  - Fregin A
FAU - Srsen, S
AU  - Srsen S
FAU - Srsnova, K
AU  - Srsnova K
FAU - Halliger-Keller, B
AU  - Halliger-Keller B
FAU - Felbor, U
AU  - Felbor U
FAU - Seemanova, E
AU  - Seemanova E
FAU - Kress, W
AU  - Kress W
LA  - eng
PT  - Journal Article
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (DNA, Complementary)
RN  - 0 (Genetic Markers)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Alkaptonuria/ethnology/*genetics
MH  - Alleles
MH  - Alternative Splicing
MH  - DNA, Complementary/analysis
MH  - Europe/epidemiology
MH  - Exons
MH  - Founder Effect
MH  - Genetic Heterogeneity
MH  - Genetic Markers
MH  - Genetic Testing
MH  - Humans
MH  - Introns
MH  - *Mutation
MH  - Mutation, Missense
MH  - Point Mutation
MH  - Polymorphism, Restriction Fragment Length
MH  - Recombinant Proteins/metabolism
MH  - Time Factors
EDAT- 1999/09/14 00:00
MHDA- 1999/09/14 00:01
CRDT- 1999/09/14 00:00
PHST- 1999/09/14 00:00 [pubmed]
PHST- 1999/09/14 00:01 [medline]
PHST- 1999/09/14 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200343 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Sep;7(6):645-51. doi: 10.1038/sj.ejhg.5200343.