Häufige erkrankungen mit repeatexpansionen

Expansions of unstable DNA repeats are causes of a growing number of human developmental and degenerative disorders. The repetitive sequences vary in copy number even in normal individuals. In affected individuals the repeat is expanded beyond a disease-specific threshold. There is some relationship between the copy number of the repeat and the severity and/or age at onset of symptoms. An earlier age of onset and a more severe clinical phenotype in subsequent generations (anticipation) is usually correlated with larger repeat size. Expanded alleles show both somatic and germ-line instability and, usually, expand rather than contract upon transmission from parent to offspring. In doing so, the sex of the transmitting parent can influence the size of the disease allele in the affected child. The unstable repeat may be located in non-coding regions or within the open reading frame of the disease gene. Depending on the intragenic location and the mode of inheritance the pathogenetic mechanisms involve loss of protein function as well as gain of function at protein or RNA level.