Ryan S G, Dixon M J, Nigro M A, Kelts K A, Markand O N, Terry J C, Shiang R, Wasmuth J J, O'Connell P
Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284.
Am J Hum Genet. 1992 Dec;51(6):1334-43.
Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. We performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region.
惊跳症，或惊吓病（STHE），是一种常染色体显性神经障碍疾病，其特征为中枢神经系统起源的肌肉僵硬，尤其是在新生儿期，以及对突然、意外的听觉或触觉刺激产生夸张的惊跳反应。STHE对作用于A型γ-氨基丁酸（GABA-A）受体的苯二氮䓬类药物氯硝西泮有显著反应。基于在一个大家庭中与集落刺激因子1受体（CSF1-R）基因座紧密连锁，最近将STHE基因座（STHE）定位到5号染色体长臂。我们用8个5号染色体长臂微卫星标记对最初的以及另外三个STHE家系进行了连锁分析，并将几个最紧密连锁的标记置于该区域现有的辐射杂种（RH）图谱上。结果为基因座同质性提供了有力证据，并将STHE定位到由CSF1-R和D5S379定义的5.9厘摩区间，它们在RH图谱上的距离为74厘雷（约2.2 - 3.7兆碱基）。两个多态性标记（D5S119和D5S209）位于该区域内，但无法相对于STHE进行排序。RH图谱分析排除了编码GABA-A受体成分的候选基因GABRA1和GABRG2，因为它们位于目标区域的端粒侧。
