Chapter 11 The CAG –polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology

Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Colleen A. Stoyas, Albert R. La Spada Throughout the genome, unstable tandem nucleotide repeats can expand to cause a variety of neurologic disorders. Expansion of a CAG triplet repeat within a coding exon gives rise to an elongated polyglutamine (polyQ) tract in the resultant protein product, and accounts for a unique category of neurodegenerative disorders, known as the CAG–polyglutamine repeat diseases. The nine members of the CAG–polyglutamine disease family include spinal and bulbar muscular atrophy (SBMA), Huntington disease, dentatorubral pallidoluysian atrophy, and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). All CAG–polyglutamine diseases are dominantly inherited, with the exception of SBMA, which is X-linked, and many CAG–polyglutamine diseases display anticipation, which is defined as increasing disease severity in successive generations of an affected kindred. Despite widespread expression of the different polyQ-expanded disease proteins throughout the body, each CAG–polyglutamine disease strikes a particular subset of neurons, although the mechanism for this cell-type selectivity remains poorly understood. While the different genes implicated in these disorders display amino acid homology only in the repeat tract domain, certain pathologic molecular processes have been implicated in almost all of the CAG–polyglutamine repeat diseases, including protein ...

Source: Handbook of Clinical Neurology - January 9, 2018 Category: Neurology Source Type: research