Dissecting the epidemiology of a trinucleotide repeat disease: example of FRDA in Finland

• Published in: Human genetics Vol. 110; no. 1; pp. 36 - 40
• Main Authors: JUVONEN, Vesa, KULMALA, Satu-Maria, IGNATIUS, Jaakko, PENTTINEN, Maila, SAVONTAUS, Marja-Liisa
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.01.2002; Berlin Springer Nature B.V; New York, NY
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diseases of striated muscles. Neuromuscular diseases; European Continental Ancestry Group - genetics; Female; Finland - epidemiology; Friedreich Ataxia - epidemiology; Friedreich Ataxia - genetics; Fundamental and applied biological sciences. Psychology; Genes, Recessive; Geography; Humans; Kidneys; Male; Malformations of the urinary system; Medical sciences; Molecular and cellular biology; Nephrology. Urinary tract diseases; Nerve Tissue Proteins - genetics; Neurology; Population Surveillance; Trinucleotide Repeat Expansion; Trinucleotide Repeats; Finland; Spermatozoa; Huntingtin; Alzheimer disease; Microsatellite DNA; Trinucleotide; Huntington disease; Instability; Germinal cell; Expansion
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-001-0642-x

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.