Factors Influencing Reduced Penetrance and Variable Expressivity in X-linked Dystonia-parkinsonism

Overview

Journal Med Genet

Publisher De Gruyter

Specialties Genetics
Medical Ethics

Date 2024 Jun 5

PMID 38835911

Authors

Jelena Pozojevic

Bjorn-Hergen von Holt

Ana Westenberger

Affiliations

Soon will be listed here.

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 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 and . 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.

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