Disease relevance of L1CAM

• We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation [1].
• Mutations in the L1CAM gene cause a highly variable neurological disease described as X-linked hydrocephalus, MASA syndrome or spastic paraplegia type I. Over one-third of the mutations identified in affected boys are missense, unique to individual families and distributed primarily across the large extracellular domain of the L1 protein [2].
• Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule [3].
• Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease [3]?
• We hypothesize that L1CAM-mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease-associated gene to cause intestinal aganglionosis [3].
• DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples [4].

Psychiatry related information on L1CAM

• MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus [5].

High impact information on L1CAM

• MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM [5].
• Three different L1CAM mutations were identified: a deletion removing part of the open reading frame and two point mutations resulting in amino acid substitutions [5].
• X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene [1].
• X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28 [1].
• One locus (SPG 1) maps to Xq28 while two clinically distinct forms map to Xq22 (SPG2) [6].

Chemical compound and disease context of L1CAM

• Inhibition of the functions of L1 cell adhesion molecule (L1) by ethanol has been implicated in the pathogenesis of the neurodevelopmental aspects of the fetal alcohol syndrome (FAS) [7].
• By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-beta-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes [8].
• A penicillin-resistant mutant, JH2-2r (MIC 75 microg ml(-1)), was isolated from Enterococcus faecalis JH2-2 (MIC 5 microg ml(-1)) by successive passages on plates containing increasing concentrations of benzylpenicillin [9].
• Z- and Fmoc-L-tetrahydrofuranylglycines have been obtained from L-vinylglycine through dipolar cycloaddition reaction, and its Fmoc derivative has been applied in the synthesis of modified S9 and S10 substrates of HIV-1 protease [10].

Biological context of L1CAM

• X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene [11].
• In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons [12].
• The two frameshift mutations (52insC and 955delG) and the nonsense mutation (Trp276Ter) most probably result in functional null alleles and complete absence of L1CAM at the cell surface [13].
• The neural cell adhesion molecule L1 (L1CAM) plays a key role during embryonic development of the nervous system and is involved in memory and learning [14].
• Molecular structure and functional testing of human L1CAM: an interspecies comparison [15].

Anatomical context of L1CAM

• These findings represented impaired L1CAM function during development of the nervous system with resultant adhesion between neurons, neurites outgrowth and fasciculation, and neural cell migration [16].
• We have characterised a rare intragenic deletion of the L1CAM gene in a sample of DNA extracted from a chorionic villus biopsy (CVB) performed at 12 weeks' gestation. =[17]
• As adhesive interactions with endothelia, leukocytes, or thrombocytes enable malignant cells to penetrate the endothelium and to circulate in blood or lymphatic vessels, we here addressed the adhesion molecules CD171 (L1CAM) and CD24, which are known to be expressed by neurons, neuroblastomas, and other malignant tumors [18].
• L1CAM, a neural cell adhesion molecule, plays an important role in the development of the central nervous system [19].
• During our genetic analysis, we have discovered that L1CAM is also expressed on the surface of B cells but that the messenger RNA in this tissue is different to that in brain through alternative splicing of the L1 gene [20].

Associations of L1CAM with chemical compounds

• The neuronal cell adhesion molecule L1 (L1CAM) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and is essential in the development of the nervous system [21].
• This mutation from adenine to guanine results in an amino acid change from lysine to glutamic acid at residue 655 of the L1CAM protein, which belongs to the fibronectin type III domain [22].
• Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine-salvage pathway and catalyzes the continuous reaction of 2,3-diketo-5-methylthio-1-phosphopentane to yield the acireductone metabolite [23].
• These findings suggest a general mechanism for the patterning of cell contact based on external signals that regulate tyrosine phosphorylation of L1CAM members and modulate their binding to ankyrin [24].
• For detection of a single-nucleotide deletion, a normally 44 bp region of the L1CAM gene was amplified in a 50 microL solution, and measurement was carried out on the DNA sample after phenol extraction and ethanol precipitation [25].

Other interactions of L1CAM

• The duplications in the four patients vary in size from 0.4 to 0.8 Mb and harbor several genes, which, for each duplication, include the MR-related L1CAM and MECP2 genes [26].
• The ALD gene has been positioned on a pulsed-field map between DXS15 and the L1CAM gene, about 650 kb upstream from the color pigment genes [27].
• Linkage analysis studies implicated the neural cell adhesion molecule L1 (L1CAM) gene as a candidate gene for these X-linked disorders [28].
• Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions [29].
• Identification of a recombination event between the HSAS gene and Xq28 loci F8C and DXS605 (2-19) reduces the size of the interval likely to contain the disease locus to about 1.5 megabases, the distance between DXS605 and DXS52 [30].

Analytical, diagnostic and therapeutic context of L1CAM

• Restriction endonuclease fingerprinting (REF) has been utilized to screen 19 of the 28 exons in the L1CAM gene using only 5 PCR reactions [31].
• Prenatal diagnosis of L1CAM gene mutations in X-linked hydrocephalus [32].
• Brainstem diffusion-weighted MRI in boys with L1CAM mutations [33].
• PGP 9.5, S100, and L1CAM immunofluorescence staining of the normal mucosa demonstrated a characteristic 3D meshlike neuronal network of uniform thickness surrounding the crypts [34].
• Ligation of the L1-CAM ectodomain by an immobile substrate induces L1CD-ankyrinB binding and the formation of stationary ankyrinB clusters [35].

References