Nolte Dagmar, Niemann Stephan, Müller Ulrich
Institut für Humangenetik, Justus-Liebig-Universität, Schlangenzahl 14, 35392 Giessen, Germany.
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10347-52. doi: 10.1073/pnas.1831949100. Epub 2003 Aug 19.
X-linked dystonia parkinsonism (XDP) is an X-linked recessive adult onset movement disorder characterized by both dystonia and parkinsonism. We report delineation of the disease gene within a 300-kb interval of Xq13.1 by allelic association. Sequencing of this region in a patient revealed five disease-specific single-nucleotide changes (here referred to as DSC) and a 48-bp deletion unique to XDP. One of the DSCs is located within an exon of a not previously described multiple transcript system that is composed of at least 16 exons. There is a minimum of three different transcription start sites that encode four different transcripts. Two of these transcripts include distal portions of the TAF1 gene (TATA-box binding protein-associated factor 1) and are alternatively spliced. Three exons overlap with ING2 (a putative tumor suppressor) and with a homologue of CIS4 (cytokine-inducible SH2 protein 4), both of which are encoded by the opposite strand. Although all DSCs are located within this multiple transcript system, only DSC3 lies within an exon. This exon is used by all alternative transcripts making a pathogenic role of DSC3 in XDP likely. The multiple transcript system is therefore referred to as DYT3 (disease locus in XDP).
X连锁肌张力障碍帕金森综合征（XDP）是一种X连锁隐性成年起病的运动障碍，其特征为肌张力障碍和帕金森综合征。我们通过等位基因关联报告了在Xq13.1的300 kb区间内对疾病基因的定位。对一名患者该区域进行测序发现了五个疾病特异性单核苷酸变化（以下称为DSC）以及一个XDP特有的48 bp缺失。其中一个DSC位于一个先前未描述的多转录本系统的外显子内，该系统由至少16个外显子组成。至少有三个不同的转录起始位点，可编码四种不同的转录本。其中两个转录本包括TAF1基因（TATA盒结合蛋白相关因子1）的远端部分，并且是可变剪接的。三个外显子与ING2（一种假定的肿瘤抑制因子）以及CIS4（细胞因子诱导的SH2蛋白4）的同源物重叠，二者均由相反链编码。尽管所有DSC都位于这个多转录本系统内，但只有DSC3位于一个外显子内。所有可变转录本都使用这个外显子，这使得DSC3在XDP中可能发挥致病作用。因此，这个多转录本系统被称为DYT3（XDP中的疾病位点）。
