Frequency of the loss of CAA interruption in the HTT CAG tract and implications for Huntington disease in the reduced penetrance range.

ABSTRACT:

Purpose

In some Huntington disease (HD) patients, the "loss of interruption" (LOI) variant eliminates an interrupting codon in the HTT CAG-repeat tract, which causes earlier age of onset (AOO). The magnitude of this effect is uncertain, since previous studies included few LOI carriers, and the variant also causes CAG size misestimation. We developed a rapid LOI detection screen, enabling unbiased frequency estimation among manifest HD patients. Additionally, we combined published data with clinical data from newly identified patients to accurately characterize the LOI's effect on AOO.

Methods

We developed a LOI detection polymerase chain reaction (PCR) assay, and screened patients to estimate the frequency of the LOI variant and its effect on AOO.

Results

Mean onset f

SUBMITTER: Findlay Black H 

PROVIDER: S-EPMC7708297 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature