title: Dissecting the epidemiology of a trinucleotide repeat disease - example of FRDA in Finland.
abstract: Friedreich ataxia (FRDA) is associated with the expansion of a GAA trinucleotide repeat in the first intron of the frataxin (X25) gene. Worldwide it is considered to be the most common form of hereditary ataxia, but it is infrequently encountered in Finland. We have performed the first epidemiological study on the frequency of FRDA in Finland by combining results from a nationwide clinical survey and a molecular carrier testing study. Haplotype analysis was performed for the Finnish FRDA patients and the distribution of frataxin gene GAA repeats was analyzed in controls. In the general population of Finland, the carrier frequency was only 1 in 500, corresponding to a birth incidence of 1 in 10(6). In the more sparsely populated Northern Finland the carrier frequency was five times higher and also four out of the seven Finnish FRDA patients originated from this region. Haplotype analysis revealed the major universal risk haplotype in all the investigated patients. Alleles in the uppermost end of the normal variation (28-36 GAA) were totally missing in the Finnish population. The relative enrichment of the FRDA mutation in the north probably dates back to the internal migration movement and inhabitation of northern Finland in the 1500s. Breaking down the epidemiology of FRDA into clinical and molecular components brings along the possibility of providing more reliable and population-based genetic counseling and recurrence risk estimations.
authors.affiliation: University of Turku, Department of Medical Genetics, Kiinamyllynkatu 10, 20520 Turku, Finland. vesa.juvonen@utu.fi
authors.forename: Vesa
authors.initials: V
authors.lastname: Juvonen
authors.forename: Satu-Maria
authors.initials: SM
authors.lastname: Kulmala
authors.forename: Jaakko
authors.initials: J
authors.lastname: Ignatius
authors.forename: Maila
authors.initials: M
authors.lastname: Penttinen
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Savontaus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D005260:Female; D005387:Finland / Q000453:epidemiology; D005621:Friedreich Ataxia / Q000453:epidemiology* / Q000235:genetics; D005808:Genes, Recessive; D005843:Geography; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011159:Population Surveillance; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats; D044465:White People / Q000235:genetics
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins