The occurrence of dominant spinocerebellar ataxias among 251 Finnish ataxia patients and the role of predisposing large normal alleles in a genetically isolated population.
OBJECTIVE
Frequency and distribution of dominant ataxias caused by dynamic mutations may vary in different populations, which has been explained on the basis of relative frequency of predisposing normal alleles. The aim of the study was to evaluate the occurrence of spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA) in Finland, and to investigate the role of predisposing normal alleles in a genetically homogenous population.


METHODS
Mutation analyses for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, and DRPLA and frataxin genes were performed for 251 unrelated Finnish patients who presented with progressive ataxia disorder.


RESULTS
Expansions of SCA1, SCA2, SCA6, SCA7, SCA8, and SCA17 genes were detected in 2, 1, 1, 7, 22, and 1 patients, respectively. Altogether, 39 and 7% of dominant and sporadic SCA patients, respectively, harboured expansions at some of the investigated loci. Normal variation, collected from 477 to 502 chromosomes at each disease loci, revealed that Finns were different from the Japanese but largely similar to other Caucasians.


CONCLUSIONS
Lack of SCA3 and excess of SCA8 are characteristic to the Finnish population. Homozygosity for the SCA8 expansion increases penetrance. Frequencies of large normal alleles at the SCA loci predict poorly prevalence of the respective diseases in Finland. Prioritization in DNA testing, based on ethnic origin and geographical location, is recommendable in Finland, and analogous approach may be applied to other countries as well.
Juvonen
V
V
Department of Medical Genetics, University of Turku, Turku, Finland. vesa.juvonen@tyks.fi
Hietala
M
M
Kairisto
V
V
Savontaus
M-L
ML
D000067696:Ataxin-1; D000067699:Ataxin-3; D000067528:Ataxins; D015220:Calcium Channels / Q000235:genetics; D042622:DNA Repeat Expansion; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D019683:Penetrance; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins; D020754:Spinocerebellar Ataxias / Q000453:epidemiology* / Q000235:genetics*; D020864:Calcium Channels, N-Type
D000067696:Ataxin-1; D000067699:Ataxin-3; D000067528:Ataxins; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; C000593749:ATXN1 protein, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C095278:atrophin-1; C092341:ATXN3 protein, human