Sossey-Alaoui K, Hartung A J, Guerrini R, Manchester D K, Posar A, Puche-Mira A, Andermann E, Dobyns W B, Srivastava A K
J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA.
Hum Mol Genet. 1998 Aug;7(8):1327-32. doi: 10.1093/hmg/7.8.1327.
Subcortical band heterotopia (SBH) and classical lissencephaly (LIS) result from deficient neuronal migration which causes mental retardation and epilepsy. A single LIS/SBH locus on Xq22.3-q24 was mapped by linkage analysis and physical mapping of the breakpoint in an X;2 translocation. A recently identified gene, doublecortin ( DCX ), is expressed in fetal brain and mutated in LIS/SBH patients. We have identified four novel missense mutations in the gene, one familial mutation with LIS in a male and SBH in the carrier females, one de novo mutation in an SBH female, and two mutations in sporadic SBH female patients. The DCX gene is found to be expressed exclusively at a very high level in the adult frontal lobe. We have also cloned the X-linked mouse doublecortin (Dcx) gene. It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca2+-dependent signaling.
皮质下带状异位（SBH）和经典型无脑回畸形（LIS）是由神经元迁移缺陷导致的，可引起智力发育迟缓及癫痫。通过对X;2易位断点进行连锁分析和物理图谱分析，将一个单一的LIS/SBH基因座定位于Xq22.3-q24。最近发现的双皮质素（DCX）基因在胎儿脑中表达，且在LIS/SBH患者中发生突变。我们在该基因中鉴定出4个新的错义突变，一个是在一名男性LIS患者及携带者女性SBH患者中的家族性突变，一个是在一名SBH女性患者中的新发突变，还有两个是散发性SBH女性患者中的突变。发现DCX基因仅在成人额叶中高水平表达。我们还克隆了X连锁的小鼠双皮质素（Dcx）基因。它编码一种高度亲水的40 kDa蛋白的异构体，与人源对应物同源，并含有几个潜在的磷酸化位点。人和小鼠的DCX蛋白均与一种含有Ca2+/钙调蛋白激酶结构域的中枢神经系统蛋白同源，这表明DCX蛋白可能属于一类通过Ca2+依赖信号传导参与神经元迁移的新型细胞内蛋白。
