des Portes V, Francis F, Pinard J M, Desguerre I, Moutard M L, Snoeck I, Meiners L C, Capron F, Cusmai R, Ricci S, Motte J, Echenne B, Ponsot G, Dulac O, Chelly J, Beldjord C
INSERM U129, Institut Cochin de Génétique Moléculaire, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Hum Mol Genet. 1998 Jul;7(7):1063-70. doi: 10.1093/hmg/7.7.1063.
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X-SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.
皮质下板层异位症（SCLH），即“双皮质综合征”，是一种与神经元迁移缺陷相关的皮质发育异常疾病。临床表现为癫痫和智力迟钝。这种疾病主要影响女性，可在单个家系中与无脑回畸形（一种影响男性个体的更严重疾病）一起遗传。这种临床实体被描述为X-SCLH/LIS综合征。最近我们证明，位于X染色体上的双皮质素基因与这种疾病有关。我们现在对11名无亲缘关系的患有SCLH的女性（1例家族性和10例散发性病例）进行了双皮质素的系统突变分析，在11例中的10例中发现了突变。序列差异包括无义突变、剪接位点突变和错义突变，这些突变在整个基因中均有发现。这些结果提供了强有力的证据，表明双皮质素功能丧失是SCLH的主要原因。表型与基因型之间缺乏相关性表明，神经元前体细胞的X染色体失活模式可能导致女性中这种疾病临床严重程度的差异。
