Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection

Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset.

The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain reg...

A role for Mlh3 in somatic hypermutation.

Somatic hypermutation (SHM) and class switch recombination (CSR) allow B cells to make high affinity antibodies of various isotypes. Both processes are initiated by activation-induced cytidine deaminase (AID) to generate dG:dU mismatches in the immunoglobulin genes that are resolved differently in SHM and CSR to introduce point mutations and recombination, respectively. The MutL homolog MLH3 ha...

Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches

The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a...

molecular analysis of the (cag)n repeat causing huntingtons disease in 66 iranian families

huntington’s disease (hd) is an inherited neurodegenerative disorder characterized by chorea and progressive dementia. the mutation causing the disease has been identified as an unstable expansion of a tri-nucleotide (cag) n at the 5 end of the it 15 gene on chromosome 4. we analyzed the distribution of cag repeats in 66 iranian patients belonging to 66 unrelated families. we found one expanded...

“Not Everything That Is Faced Can Be Changed, but Nothing Can Be Changed Until It Is Faced”: A Response to Recent Commentaries