Nolte D, Ramser J, Niemann S, Lehrach H, Sudbrak R, Müller U
Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
Neurogenetics. 2001 Oct;3(4):207-13. doi: 10.1007/s100480100120.
We searched for novel genes as candidates of X-linked dystonia parkinsonism (XDP) in the critical interval of Xq13.1 that harbors the disease locus (DYT3). A gene, ACRC (acidic repeat containing), was discovered by a combination of in silico and "wet" experiments. ACRC is composed of at least 12 exons and 11 introns. It is expressed in all tissues tested, including skeletal muscle, liver, kidney, pancreas, heart, lung, and brain. Highest levels of expression are found in skeletal muscle. The ACRC protein is characterized by a previously undescribed acidic repeat tract of 21 units of 8-10 amino acids. The N-terminal portion of the protein is highly acidic (pI=3.2), and the C-terminal region is basic (pI=10.2). There are nuclear localization signals in its C-terminal portion. Extensive mutation analysis of the transcribed region of the gene, including intron-exon boundaries and the 5' and 3' untranslated intervals, did not reveal a mutation in XDP patients. Exclusion of a mutation in the transcribed portion of this and all other known genes within the DYT3 critical interval suggests that XDP is most likely caused by a mutation in a regulatory region of a gene within the critical interval, or by a structural rearrangement.
我们在包含疾病基因座（DYT3）的Xq13.1关键区间寻找作为X连锁肌张力障碍帕金森综合征（XDP）候选基因的新基因。通过计算机模拟和“湿实验”相结合的方法发现了一个名为ACRC（含酸性重复序列）的基因。ACRC由至少12个外显子和11个内含子组成。它在所有检测的组织中均有表达，包括骨骼肌、肝脏、肾脏、胰腺、心脏、肺和脑。在骨骼肌中发现其表达水平最高。ACRC蛋白的特征是具有一个由21个8 - 10个氨基酸单位组成的、以前未描述过的酸性重复序列。该蛋白的N端部分高度酸性（pI = 3.2），C端区域呈碱性（pI = 10.2）。其C端部分存在核定位信号。对该基因转录区域进行广泛的突变分析，包括内含子与外显子边界以及5'和3'非翻译区间，未在XDP患者中发现突变。排除DYT3关键区间内该基因及所有其他已知基因转录部分的突变表明，XDP很可能是由关键区间内某个基因的调控区域突变或结构重排引起的。
