A research team has developed a novel measure of disease progression for Huntington’s disease (HD), enabling them to identify a genetic modifier associated with how rapidly the disease progresses.

The study was published in Lancet Neurology.

HD is a fatal neurological disease caused by a genetic mutation. Larger mutations are linked to rapidly progressing disease, but that does not account for all aspects of disease progression.

The research team used the high-quality phenotypic data from the intensively studied TRACK-HD cohort of people with the HD gene mutation. They established that different symptoms of disease progress in parallel, so they were able to combine the data from 24 cognitive, motor and MRI brain imaging variables to generate their progression score for genetic analysis.

They then looked for areas of the genome associated with their progression measure, and found a significant result in their sample of 216 people, which they then validated in a larger sample of 1773 people from a separate cohort, the European Huntington’s Disease Network (EHDN) REGISTRY study.

The genetic signal is likely to be driven by the gene MSH3, a DNA repair gene which has been linked to changes in size of the HD mutation. The researchers identified that a variation in MSH3 encodes an amino acid change in the gene. MSH3 has previously been extensively implicated in the pathogenesis of HD in both mouse and cell studies. The group’s findings may also be relevant to other diseases caused by repeats in the DNA, including some spinocerebellar ataxias.

Paper: “Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study”
Reprinted from materials provided by University College London.

20 Ιουλίου, 2017