Abstract
Morphological alterations in the brains of schizophrenia patients suggest that neurodevelopmental dysfunction is involved in the etiology of the disease.1 Such dysfunction may be due to functional alterations of cell adhesion molecules, which play important roles in cell migration, axonal growth, fasciculation, synaptogenesis, and synaptic remodeling. We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia. A missense polymorphism (Leu17Phe) in the signal peptide region was identified. A case-control comparison revealed significantly higher frequencies of the Leu/Leu genotype (P = 0.004) and the Leu allele (P = 0.006) in 282 Japanese schizophrenic patients than in 229 Japanese control subjects. The estimated odds ratio for schizophrenia was 1.83 (95% CI, 1.28–2.26) for the Leu/Leu genotype compared with the other genotypes. An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia.
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References
Harrison PJ Schizophrenia: a disorder of neurodevelopment? Curr Opin Neurobiol 1997 7 285 289
Demyanenko GP Tsai AY Maness PF Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice J Neurosci 1999 19 4907 4920
Conrad AJ Scheibel AB Schizophrenia and the hippocampus: the embryological hypothesis extended Schizophr Bull 1987 13 577 587
Poltorak M Wright R Hemperly JJ Torrey EF Issa F Wyatt RJ et alMonozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF Brain Res 1997 751 152 154
van Kammen DP Poltorak M Kelley ME Yao JK Gurklis JA Peters JL et alFurther studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia Biol Psychiatry 1998 43 680 686
Vawter MP Cannon-Spoor HE Hemperly JJ Hyde TM VanderPutten DM Kleinman JE et alAbnormal expression of cell recognition molecules in schizophrenia Exp Neurol 1998 149 424 432
Webster MJ Vawter MP Freed WJ Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex patients with schizophrenia, bipolar disorder, and depression Mol Psychiatry 1999 4 46 52
Vawter MP Dysregulation of the neural cell adhesion molecule and neuropsychiatric disorders Eur J Pharmacol 2000 405 385 395
Cannon TD Mednick SA Parnas J Schulsinger F Praestholm J Vestergaard A Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors Arch Gen Psychiatry 1993 50 551 564
Cannon TD Rosso IM Hollister JM Bearden CE Sanchez LE Hadley T A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia Schizophr Bull 2000 26 351 366
Vicente AM Macciardi F Verga M Bassett AS Honer WG Bean G et alNCAM and schizophrenia: genetic studies Mol Psychiatry 1997 2 65 69
Kurumaji A Nomoto H Okano T Toru M An association study between polymorphisms of L1CAM gene and schizophrenia in a Japanese sample Am J Med Genet 2001 105 99 104
Brummendorf T Rathjen FG Cell adhesion molecules. 1: immunoglobulin superfamily Protein Profile 1994 1 951 1058
Holm J Hillenbrand R Steuber V Bartsch U Moos M Lubbert H et alStructural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules Eur J Neurosci 1996 8 1613 1629
Hillenbrand R Molthagen M Montag D Schachner M The close homologue of the neural adhesion molecule L1 (CHL1): patterns of expression and promotion of neurite outgrowth by heterophilic interactions Eur J Neurosci 1999 11 813 826
Faraone SV Matise T Svrakic D Pepple J Malaspina D Suarez B et alGenome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium Am J Med Genet 1998 81 290 295
Levinson DF Mahtani MM Nancarrow DJ Brown DM Kruglyak L Kirby A et alGenome scan of schizophrenia Am J Psychiatry 1998 155 741 750
Hovatta I Lichtermann D Juvonen H Suvisaari J Terwilliger JD Arajarvi R et alLinkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set Mol Psychiatry 1998 3 452 457
Shaw SH Kelly M Smith AB Shields G Hopkins PJ Loftus J et alA genome-wide search for schizophrenia susceptibility genes Am J Med Genet 1998 81 364 376
von Heijne G The signal peptide J Membr Biol 1990 115 195 201
Jouet M Moncla A Paterson J McKeown C Fryer A Carpenter N et alNew domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome Am J Hum Genet 1995 56 1304 1314
Fujita Y Nakata K Yasui N Matsui Y Kataoka E Hiroshima K et alNovel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterization J Clin Endocrinol Metab 2000 85 425 431
Arnold A Horst SA Gardella TJ Baba H Levine MA Kronenberg HM Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism J Clin Invest 1990 86 1084 1087
Seppen J Steenken E Lindhout D Bosma PJ Elferink RP A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler–Najjar type II FEBS Lett 1996 390 294 298
Cragg H Williamson M Young E O'Brien J Alhadeff J Fang-Kircher S et alFucosidosis: genetic and biochemical analysis of eight cases J Med Genet 1997 34 105 110
Acknowledgements
This study was supported by grants from Ministry of Education, Culture, Sports, Science and Technology (No. 12204001) and the grant for Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare of Japan.
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Sakurai, K., Migita, O., Toru, M. et al. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol Psychiatry 7, 412–415 (2002). https://doi.org/10.1038/sj.mp.4000973
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DOI: https://doi.org/10.1038/sj.mp.4000973
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