Tijssen M A, Shiang R, van Deutekom J, Boerman R H, Wasmuth J J, Sandkuijl L A, Frants R R, Padberg G W
Department of Neurology, University Hospital Leiden, The Netherlands.
Arch Neurol. 1995 Jun;52(6):578-82. doi: 10.1001/archneur.1995.00540300052012.
To confirm linkage of the locus of the major form of hyperekplexia to markers on chromosome 5q, to screen for a point mutation in the gene encoding the alpha 1 subunit of the glycine receptor, and to investigate whether the putative "minor" form of hyperkeplexia consisting of an excessive startle response without stiffness, is based on the same genetic defect as the major form.
A survey of various symptoms of hyperekplexia was performed in the Dutch pedigree. Linkage studies were performed for these symptoms.
Subjects were visited at home, and the genetic study was performed at University Hospital Leiden, (the Netherlands).
A history was taken from 76 subjects in the pedigree, and neurologic examinations were performed on 61 subjects from four generations of the pedigree.
The main outcome measures were lod scores for markers on chromosome 5q for the major and minor forms of hyperekplexia and periodic leg movements during sleep. Mutations in the alpha 1 subunit of the glycine receptor were detected by screening the exons with denaturing gradient gel electrophoresis.
Exaggerated startle responses were reported in 44 patients. The major form consisted of stiffness in addition to the excessive startle reaction and occurred in 28 subjects. Sixteen of 44 subjects had startle responses without stiffness, indicating the minor form. Linkage was found between markers CSF1-R, D5S209, and D5S119 and the disease locus for the major form, but not for the minor form. The alpha 1 subunit of the glycine receptor showed a G to A transition mutation in codon 271 for the major form, but not for the minor form.
Linkage and an abnormal glycine receptor were found only in the major form of hyperekplexia. Recognition of a major form is based on additional stiffness. This is therefore the most important diagnostic symptom. The minor form is not a different expression of the same genetic defect and may represent a normal but pronounced startle response.
确认僵人综合征主要类型的基因座与5号染色体q臂上标记物的连锁关系，筛查甘氨酸受体α1亚基编码基因中的点突变，并研究由过度惊吓反应但无僵硬症状组成的假定“轻微”型僵人综合征是否与主要类型基于相同的遗传缺陷。
对荷兰家系中僵人综合征的各种症状进行调查。对这些症状进行连锁研究。
在家中对受试者进行访视，基因研究在荷兰莱顿大学医学中心进行。
采集了家系中76名受试者的病史，并对来自该家系四代的61名受试者进行了神经学检查。
主要观察指标是僵人综合征主要和轻微类型以及睡眠中周期性腿部运动的5号染色体q臂上标记物的对数优势分数。通过变性梯度凝胶电泳筛查外显子来检测甘氨酸受体α1亚基中的突变。
44例患者报告有夸张的惊吓反应。主要类型除过度惊吓反应外还包括僵硬，发生在28名受试者中。44名受试者中有16名有惊吓反应但无僵硬症状，表明为轻微类型。在标记物CSF1-R、D5S209和D5S119与主要类型的疾病基因座之间发现了连锁关系，但与轻微类型未发现连锁关系。甘氨酸受体α1亚基在主要类型中密码子271处出现了G到A的转换突变，但在轻微类型中未出现。
仅在僵人综合征的主要类型中发现了连锁关系和异常的甘氨酸受体。主要类型的识别基于额外的僵硬症状。因此，这是最重要的诊断症状。轻微类型不是相同遗传缺陷的不同表现，可能代表正常但明显的惊吓反应。
