Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.

The galectin-1 gene is a developmentally regulated gene whose activity is strongly modulated during cell differentiation and transformation. We have previously shown that galectin-1 promoter constructs are highly active when transiently transfected in cells both expressing and not expressing the endogenous gene and that the basal activity is determined by a small region encompassing the transcription start site (from positions ؊50 to ؉50). We have now investigated the role of DNA methylation in galectin-1 gene expression. Southern blot analysis with HpaII and MspI endonucleases and sodium bisulfite analysis of genomic DNA from expressing and nonexpressing cell lines and cell hybrids showed a close correlation between gene activity and demethylation of the 5 region of the galectin-1 gene. We found that the galectin-1 promoter region is fully methylated, at every CpG site on both strands, in nonexpressing differentiated rat liver (FAO) and thyroid (PC Cl3) cells and unmethylated in the expressing undifferentiated liver (BRL3A) and thyroid transformed (PC myc/raf) cell lines. In addition, reactivation of the silent FAO alleles in the FAO-human osteosarcoma (143TK ؊ ) hybrid cells is accompanied by a complete demethylation of the promoter region. Finally, when galectin-1-chloramphenicol acetyltransferase (CAT) promoter constructs were methylated in vitro by SssI methylase at every cytosine residue of the CpG doublets and transfected into mouse fibroblasts, the transcription of the CAT reporter gene was strongly inhibited.Mammalian lectins are a growing class of proteins that share the presence of a carbohydrate recognition domain and are involved in several biological processes (17). Changes in the expression of endogenous lectins and abnormal glycosylation may both result in altered protein-carbohydrate interactions and are characteristic of a number of diseases, including autoimmune diseases and cancer (17). In this work, we investigated whether changes in DNA methylation, which are frequently associated with differentiation and transformation events (28, 43), can account for variations in the expression of the endogenous lectin galectin-1 (2, 3).Galectin-1 appears to play a key role in different biological processes, such as cell growth control (37, 40, 51, 52), cell-cell and cell-matrix interactions, including acquisition of the metastatic phenotype (14,22,34,50), and the maturation of Tlymphoblastoid cells (5). The expression of galectin-1 is strongly modulated during development (38) and increases dramatically with transformation and loss of differentiated functions both in cell lines (10, 41) and in mammalian tissues (9, 27). By contrast, treatment of transformed neural cells with differentiating agents leads to extinction of galectin-1 expression (7, 33). Nuclear run-on experiments showed that regulation of this gene occurs, at least in part, at the transcriptional level (10). To date, however, little is known concerning the mechanisms whereby transformation and loss of differentiation lead to transcriptiona...

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Cranioectodermal dysplasia is a rare syndrome characterized by craniofacial and skeletal anomalies and ectodermal dysplasia. Life-threatening associated conditions (i.e., kidney failure and abnormal regulation of the parathyroid-bone axis) can also develop. We report a patient whose features are suggestive of an inapparent, subtle phenotype of the syndrome. The patient is a 4-year-old girl with only dolichocephaly and clinodactyly; microdontia, hypodontia, and taurodontia (i.e., cone-shaped teeth); anteverted nares, full cheeks, and everted lower lip; epicanthal folds, hypertelorism and hyperopia; and corpus callosum hypoplasia. She has no rhizomelic limb shortening or hair abnormalities. In view of the rarity of the cranioectodermal dysplasias, the variability of the phenotype, and the uncertain outcome of some previously described patients, we believe this inapparent, subtle case should reported to enable better understanding and treatment of this rare syndrome.