8afp

Structural highlights

Disease

L1CAM_HUMAN Hydrocephalus with stenosis of the aqueduct of Sylvius;MASA syndrome;X-linked complicated spastic paraplegia type 1;X-linked complicated corpus callosum dysgenesis. The disease is caused by variants affecting the gene represented in this entry. L1CAM mutations have also been found in few patients affected by hydrocephalus with Hirschsprung disease, suggesting a role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease (PubMed:22344793).^[1] The disease is caused by variants affecting the gene represented in this entry. Defects in L1CAM may contribute to Hirschsprung disease by modifying the effects of Hirschsprung disease-associated genes to cause intestinal aganglionosis.^[2] The disease is caused by variants affecting the gene represented in this entry. Defects in L1CAM are associated with a wide phenotypic spectrum which varies from severe hydrocephalus and prenatal death (HYCX) to a milder phenotype (MASA). These variations may even occur within the same family. Due to the overlap of phenotypes between HYCX and MASA, many authors use the general concept of L1 syndrome which covers both ends of the spectrum.^{[3] [4] [5]}

Function

L1CAM_HUMAN Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity.^[6]

References

1. ↑ Fernández RM, Núñez-Torres R, García-Díaz L, de Agustín JC, Antiñolo G, Borrego S. Association of X-linked hydrocephalus and Hirschsprung disease: report of a new patient with a mutation in the L1CAM gene. Am J Med Genet A. 2012 Apr;158A(4):816-20. PMID:22344793 doi:10.1002/ajmg.a.35244
2. ↑ Parisi MA, Kapur RP, Neilson I, Hofstra RM, Holloway LW, Michaelis RC, Leppig KA. Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease? Am J Med Genet. 2002 Feb 15;108(1):51-6. PMID:11857550 doi:10.1002/ajmg.10185
3. ↑ Vos YJ, de Walle HE, Bos KK, Stegeman JA, Ten Berge AM, Bruining M, van Maarle MC, Elting MW, den Hollander NS, Hamel B, Fortuna AM, Sunde LE, Stolte-Dijkstra I, Schrander-Stumpel CT, Hofstra RM. Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling and mutation analysis. J Med Genet. 2010 Mar;47(3):169-75. PMID:19846429 doi:10.1136/jmg.2009.071688
4. ↑ Marx M, Diestel S, Bozon M, Keglowich L, Drouot N, Bouché E, Frebourg T, Minz M, Saugier-Veber P, Castellani V, Schäfer MK. Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus. Neurogenetics. 2012 Feb;13(1):49-59. PMID:22222883 doi:10.1007/s10048-011-0307-4
5. ↑ Christaller WA, Vos Y, Gebre-Medhin S, Hofstra RM, Schäfer MK. L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains. Clin Genet. 2017 Jan;91(1):115-120. PMID:26891472 doi:10.1111/cge.12763
6. ↑ Schäfer MK, Nam YC, Moumen A, Keglowich L, Bouché E, Küffner M, Bock HH, Rathjen FG, Raoul C, Frotscher M. L1 syndrome mutations impair neuronal L1 function at different levels by divergent mechanisms. Neurobiol Dis. 2010 Oct;40(1):222-37. PMID:20621658 doi:10.1016/j.nbd.2010.05.029
7. ↑ Guédez G, Loers G, Jeffries CM, Kozak S, Meijers R, Svergun DI, Schachner M, Löw C. X-ray structure and function of fibronectin domains two and three of the neural cell adhesion molecule L1. FASEB J. 2023 Mar;37(3):e22823. PMID:36809668 doi:10.1096/fj.202201511R