Rees M, Curtis D, Parker K, Sundqvist A, Baralle D, Bespalova I N, Burmeister M, Chung E, Gardiner R M, Whitehouse W P
Department of Paediatrics, University College London Medical School, Rayne Institute, UK.
Neuropediatrics. 1994 Feb;25(1):20-5. doi: 10.1055/s-2008-1071576.
The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.
昂韦里希特-伦德伯格病（EPM 1）的基因座最近已被定位于21号染色体的21q22.3区域。在患有青少年肌阵挛性癫痫的先证者家族中，一个与特发性全身性癫痫易感性相关的基因座EJM 1，通过与HLA区域的连锁证据被定位于6号染色体的6p区域。然而，分离分析提示青少年肌阵挛性癫痫存在双基因座模型，并且已获得证据表明青少年肌阵挛性癫痫/特发性全身性癫痫表型内存在遗传异质性。因此，在不显示与6号染色体p臂上标记连锁的特发性全身性癫痫和青少年肌阵挛性癫痫分离家族组中，对EPM 1作为候选基因座进行了研究。使用围绕EPM 1基因区域的三个微卫星DNA标记，在25个家族中采用不同的遗传模型进行连锁分析。在四个测试模型中的三个模型下，多点连锁分析明确排除了距离EPM 1最近的连锁标记PFKL周围20厘摩的区域。这些结果强烈提示EPM 1基因与这些家族中表达的表型不连锁，因此昂韦里希特-伦德伯格病和青少年肌阵挛性癫痫不是等位基因变异。
