Jouet M, Strain L, Bonthron D, Kenwrick S
Department of Medicine, University of Cambridge, UK.
J Med Genet. 1996 Mar;33(3):248-50. doi: 10.1136/jmg.33.3.248.
X linked recessive hydrocephalus is the most common hereditary form of hydrocephalus. Genetic analysis indicates that the majority of cases are caused by mutations in a single gene in Xq28, recently identified as the gene for neural cell adhesion molecule L1. Genetic heterogeneity for this disorder was suggested following the description of a single large pedigree where X linked hydrocephalus showed lack of linkage to Xq28 markers flanking the L1 gene. Mutation analysis in this family shows a single base pair deletion within the coding sequence of the L1 gene that would result in truncation of the mature protein. The nature of the mutation and its segregation with the disease through the pedigree indicate that it is the cause of X linked hydrocephalus in this family. These results are at odds with data obtained through segregation of alleles for markers flanking the L1 gene. Somatic and germline mosaicism is the most plausible explanation for these data, which also provide further evidence for genetic homogeneity of X linked hydrocephalus.
X连锁隐性脑积水是最常见的遗传性脑积水形式。基因分析表明，大多数病例是由位于Xq28的一个单基因突变引起的，该基因最近被确定为神经细胞黏附分子L1的基因。在描述了一个大型家系后，提示了这种疾病的遗传异质性，在该家系中，X连锁脑积水显示与L1基因侧翼的Xq28标记缺乏连锁。对这个家系的突变分析显示，L1基因编码序列内有一个单碱基对缺失，这将导致成熟蛋白的截短。突变的性质及其在整个家系中与疾病的分离表明，它是这个家系中X连锁脑积水的病因。这些结果与通过L1基因侧翼标记的等位基因分离获得的数据不一致。体细胞和生殖细胞镶嵌现象是对这些数据最合理的解释，这也为X连锁脑积水的遗传同质性提供了进一步的证据。
