{Reference Type}: Journal Article
{Title}: Factors influencing reduced penetrance and variable expressivity in X-linked dystonia-parkinsonism.
{Author}: Pozojevic J;von Holt BH;Westenberger A;
{Journal}: Med Genet
{Volume}: 34
{Issue}: 2
{Year}: 2022 Jun
{Factor}: 0.836
{DOI}: 10.1515/medgen-2022-2135
{Abstract}: X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder that primarily affects adult Filipino men. It is caused by a founder retrotransposon insertion in TAF1 that contains a hexanucleotide repeat, the number of which differs among the patients and correlates with the age at disease onset (AAO) and other clinical parameters. A recent work has identified additional genetic modifiers of age-associated penetrance in XDP, bringing to light the DNA mismatch repair genes MSH3 and PMS2. Despite X-linked recessive inheritance, a minor subset of patients are female, manifesting the disease via various mechanisms such as homozygosity, imbalanced X-chromosome inactivation, or aneuploidy. Here, we summarize and discuss clinical and genetic aspects of XDP, with a focus on variable disease expressivity as a consequence of subtle genetic differences within a seemingly homogenous population of patients.