Cholestasis Familiaris Groenlandica/Byler-like disease in Greenland--a population study.
OBJECTIVE
Cholestasis Familiaris Groenlandica (CFG, or progressive familiar intrahepatic cholestasis type 1 (PFIC1)) is a very common lethal recessive inherited disease in Greenland. A missense mutation, 1660G>A (asp554asn) in the gene ATP8B1 causes the disease (Klomp et al. 2000).


METHODS
A family study examining medical files from the period 1951-2003 from East Greenland resulted in 46 cases of PFIC1 and more than 220 relatives showing carrier status. Further, random blood sample testing 953 anonymous persons from 11 major cities or districts all over Greenland have been analysed for carrier status of the mutation.


METHODS
A sensitive PCR method is developed to distinguish between normal and mutant alleles for ATP8B1 in the Greenland population.


RESULTS
The mutation 1660G>A is found in all areas of Greenland, and the frequency of the mutant allele vary all over the country. A shockingly high frequency for the mutant allele is found in East Greenland in Ittoqqortoormiit (0.16) and in Tasiilaq (0.077), whereas in Northwest Greenland lower frequencies are found in Uummannaq and Ilulissat (0.032), and Maniitsoq (0.005).


CONCLUSIONS
The high frequency of the mutation in East and Northwest Greenland strongly indicates that routine screening of the population for carrier status should be done.
Eiberg
H
H
Institute of Medical Biochemistry and Genetics, Panum Inst., University of Copenhagen, Denmark. he@imbg.ku.dk
Nørgaard-Pedersen
B
B
Nielsen
I M
IM
D000251:Adenosine Triphosphatases / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D002779:Cholestasis / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D017931:DNA Primers; D005808:Genes, Recessive; D006116:Greenland / Q000453:epidemiology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011159:Population Surveillance; D012680:Sensitivity and Specificity
D017931:DNA Primers; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human