Lehesjoki A E, Koskiniemi M, Sistonen P, Miao J, Hästbacka J, Norio R, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Finland.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3696-9. doi: 10.1073/pnas.88.9.3696.
Progressive myoclonus epilepsy of Univerricht-Lundborg type is a clinically defined entity among the progressive myoclonus epilepsies. It is an autosomal recessive disorder. The underlying biochemical defect is unknown. We used linkage analysis to localize the gene in 12 families with the aid of polymorphic DNA markers. Close linkage was detected with three markers on distal chromosome 21. The loci BCEI and D21S154 gave the highest positive logarithm-of-odds (lod) scores of 5.49 and 4.25, respectively, at zero recombination. The third locus, D21S112, gave a lod score of 6.91 at a recombination fraction of 0.034. There was no evidence of heterogeneity. Multipoint lod scores calculated against a fixed map of the three marker loci gave a maximum four-point lod score of 10.08 at a location of the disease gene at 6.0 centimorgans distal to locus BCEI and 0.8 centimorgan proximal to locus D21S154. As markers BCEI and D21S154 have previously been localized to 21q22.3 by physical methods, our findings place the EMP1 gene locus (for progressive myoclonus epilepsy of the Unverricht-Lundborg type) in chromosome 21 band q22.3. This finding provides an opportunity to test several other epilepsy phenotypes, particularly the so-called Ramsay Hunt syndrome, for linkage to the same locus. It also is a starting point toward isolating and characterizing the gene and its protein product.
昂韦里希特-伦德伯格型进行性肌阵挛癫痫是进行性肌阵挛癫痫中一个临床定义的实体。它是一种常染色体隐性疾病。潜在的生化缺陷尚不清楚。我们借助多态性DNA标记，通过连锁分析对12个家系中的该基因进行定位。在21号染色体远端的三个标记处检测到紧密连锁。位点BCEI和D21S154在零重组时分别给出了最高的正对数优势（lod）分数，即5.49和4.25。第三个位点D21S112在重组率为0.034时给出的lod分数为6.91。没有异质性的证据。针对这三个标记位点的固定图谱计算的多点lod分数，在疾病基因位于位点BCEI远端6.0厘摩、位点D21S154近端0.8厘摩的位置时，给出了最大的四点lod分数10.08。由于标记BCEI和D21S154此前已通过物理方法定位到21q22.3，我们的发现将昂韦里希特-伦德伯格型进行性肌阵挛癫痫的EMP1基因位点定位在21号染色体q22.3带。这一发现为检测其他几种癫痫表型，特别是所谓的拉姆齐·亨特综合征，是否与同一基因座连锁提供了机会。它也是分离和鉴定该基因及其蛋白质产物的起点。
