PDF(Pubmed)
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.
摘要：
X连锁肌张力障碍-帕金森病（XDP）是一种神经退行性运动障碍，主要影响成年菲律宾男性。它是由包含六核苷酸重复的TAF1中的创始人逆转录转座子插入引起的，其数量在患者中不同,并与发病年龄(AAO)和其他临床参数相关.最近的一项工作已经确定了XDP中与年龄相关的外显率的其他遗传修饰因子，照亮DNA错配修复基因MSH3和PMS2。尽管有X连锁隐性遗传,一小部分患者是女性，通过纯合性等各种机制表现疾病，不平衡的X染色体失活,或者非整倍性。这里,我们总结和讨论XDP的临床和遗传方面，由于看似同质的患者群体中细微的遗传差异，因此关注可变的疾病表达能力。
