Journal of Medical Genetics vol:32 issue:7 pages:549-52
The suggestion that the three X linked syndromes X linked spastic paraplegia (MIM 312900), MASA syndrome (MIM 303350), and X linked hydrocephalus owing to stenosis of the aqueduct of Sylvius (MIM 307000) are variable clinical manifestations of mutations at the same locus at Xq28 was confirmed by the finding of mutations in the L1-CAM gene in the three syndromes. Recently, two families in which different subjects showed a clearly different phenotype within the same family of the three X linked syndromes were described. A reverse transcription PCR assay was developed for the analysis of the L1-CAM cDNA in two of the members of these families. RNA isolated from EBV transformed cell lines and a colon carcinoma derived cell line was used as a starting material. The L1-CAM cDNA of two male patients from each family was sequenced. We report two new mutations in the L1-CAM gene in these two families showing that the three different phenotypes observed in different generations within the same family are variable phenotypic expressions of the same mutation.