The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.

ABSTRACT: Extended CAG trinucleotide repeats (TNR) in the genes huntingtin (HTT) and androgen receptor (AR) are the cause of two progressive neurodegenerative disorders: Huntington's disease (HD) and Spinal and Bulbar Muscular Atrophy (SBMA), respectively. Anyone who inherits the mutant gene in the complete penetrance range (>39 repeats for HD and 44 for SBMA) will develop the disease. An inverse correlation exists between the length of the CAG repeat and the severity and age of onset of the diseases. Growing evidence suggests that it is the length of uninterrupted CAG repeats in the mRNA rather than the length of poly glutamine (polyQ) in mutant (m)HTT protein that determines disease progression. One variant of mHTT (loss of inhibition; LOI) causes a 25 year earlier onset of HD when compared to a r

SUBMITTER: Murmann AE 

PROVIDER: S-EPMC9803637 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature