Expanded repeat sequences and disease.
The clinical phenomenon of an earlier age of onset or a more severe phenotype in later generations of a family has been termed anticipation. In a number of neurological and neuropsychiatric disorders, the anticipation has been linked to expanded repeat sequences that increase in size upon transmission. This novel mutational mechanism has been demonstrated in more than 15 disorders today. The repeat sequence motif (base composition), size, and localization of expanded repeats within the respective disease genes vary between disorders and influence the way the repeat causes disease. Here, we review the occurrence and properties of repeats in the genome. The different groups of disorders and possible pathogenic mechanisms are summarized. In addition, methods used for detection and identification of expanded repeats and the related disorders are discussed.
Neurogenetics Unit, Department of Molecular Medicine, Karolinska Institute and Hospital, Stockholm, Sweden.
K
K
Lindblad
M
M
Schalling
D020132:Anticipation, Genetic; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D018911:Trinucleotide Repeats