CRASH syndrome: Mutations in L1CAM correlate with severity of the disease
CRASH syndrome: Mutations in L1CAM correlate with severity of the disease
复制标题
DOI：
10.1055/s-2007-973696
复制
发表时间：
1997-06-01
期刊：
影响因子：
1.4
通讯作者：
Lemmon, V
中科院分区：
文献类型：
--
作者：
Yamasaki, M;Thompson, P;Lemmon, V
目前已知X连锁脑积水、MASA综合征和某些形式的X连锁痉挛性截瘫以及胼胝体发育不全是由于神经细胞粘附分子L1基因突变所致（19，30）。因此，这些综合征最近被重新归类为CRASH综合征，这是胼胝体发育不全、发育迟缓、拇指内收、痉挛和脑积水的首字母缩写（8）。现有病例报告与分子遗传学分析的比较揭示了L1CAM基因突变类型与疾病严重程度之间的显著相关性。在L1蛋白的细胞外结构域中产生截短的突变比在细胞外结构域中的点突变或仅影响蛋白质的胞质结构域的突变更可能产生严重脑积水、严重精神发育迟滞或早死。虽然没有细胞外截短那么严重，但细胞外结构域的点突变确实比细胞质结构域的突变产生更严重的神经系统问题。
X-linked hydrocephalus, MASA syndrome and certain forms of X-linked spastic paraplegia and agenesis of corpus callosum are now known to be due to mutations in the gene for the neural cell adhesion molecule L1 (19, 30). As a result, these syndromes have recently been reclassified as CRASH syndrome, an acronym for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spasticity and Hydrocephalus (8). A comparison of existing case reports with molecular genetic analysis reveals a striking correlation between the type of mutation in the L1CAM gene and the severity of the disease. Mutations that produce truncations in the extracellular domain of the L1 protein are more likely to produce severe hydrocephalus, grave mental retardation or early death than point mutations in the extracellular domain or mutations affecting only the cytoplasmic domain of the protein. While less severe than extracellular truncations, point mutations in the extracellular domain do produce more severe neurologic problems than mutations in just the cytoplasmic domain.