Summary
Since the early 1990s, a new class of molecular disease has been characterized based upon the presence of unstable and abnormal expansions of DNA-triplets (trinucleotides). The first triplet disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. At this point, there are from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome in these patients, as compared with 60 to 230 repeats in carriers and 5 to 54 repeats in unaffected individuals. The chromosomal instability resulting from this trinucleotide expansion presents clinically as mental retardation, distinctive facial features, and macroorchidism in males. The second, related DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. Identifying trinucleotide repeats as the basis of disease has brought clarity to our understanding of a complex set of inherited neurological diseases.
As more repeat expansion diseases have been discovered, several categories have been established to group them based upon similar characteristics. Category I includes Huntington's disease (HD) and the spinocerebellar ataxias that are caused by a CAG repeat expansion in protein-coding portions of specific genes. Category II expansions tend to be more phenotypically diverse with heterogeneous expansions that are generally small in magnitude, but also found in the exons of genes. Category III includes fragile X syndrome, myotonic dystrophy, two of the spinocerebellar ataxias, juvenile myoclonic epilepsy, and Friedreich's ataxia. These diseases are characterized by typically much larger repeat expansions than the first two groups, and the repeats are located outside of the protein-coding regions of the genes.
Read more about this topic: Trinucleotide Repeat Disorders
Famous quotes containing the word summary:
“Product of a myriad various minds and contending tongues, compact of obscure and minute association, a language has its own abundant and often recondite laws, in the habitual and summary recognition of which scholarship consists.”
—Walter Pater (1839–1894)
“I have simplified my politics into an utter detestation of all existing governments; and, as it is the shortest and most agreeable and summary feeling imaginable, the first moment of an universal republic would convert me into an advocate for single and uncontradicted despotism. The fact is, riches are power, and poverty is slavery all over the earth, and one sort of establishment is no better, nor worse, for a people than another.”
—George Gordon Noel Byron (1788–1824)