Skip to main content
    • Aa
    • Aa
  • The International Journal of Neuropsychopharmacology, Volume 12, Issue 1
  • February 2009, pp. 1-10

Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism

  • Tetsuya Marui (a1) (a2), Ikuko Funatogawa (a3), Shinko Koishi (a4), Kenji Yamamoto (a5), Hideo Matsumoto (a6), Ohiko Hashimoto (a7), Eiji Nanba (a8), Hisami Nishida (a9), Toshiro Sugiyama (a4), Kiyoto Kasai (a1), Keiichiro Watanabe (a10), Yukiko Kano (a10) and Nobumasa Kato (a1)
  • DOI:
  • Published online: 01 July 2008

Autism is a severe neurodevelopmental disorder of early childhood. Genetic factors play an important role in the aetiology of the disorder. In this study, we considered the NRCAM gene as a candidate gene of autism. This gene is expressed in the central nervous system and located in the 7q region, a susceptibility locus of autism. We conducted a case-control study of 18 single nucleotide polymorphisms (SNPs) within the NRCAM gene for possible association with autism in 170 autistic patients and 214 normal controls in a Japanese population. Seven SNPs in the NRCAM gene were significantly associated with autism, among which rs2300045 indicated the most prominent result (p=0.0009 uncorrected, p=0.017 corrected). In haplotype analyses, several individual haplotypes, including a common NRCAM haplotype C-T-T-C-T-T-G-C for rs3763463, rs1859767, rs1034825, rs2300045, rs2300043, rs2300039, rs722519, and rs2216259, showed a significant association after Bonferroni correction (p=0.0035 uncorrected, p=0.028 corrected). These haplotypes were located in the 5′ intron-2 region of the gene. In addition, we also assessed the above mentioned SNPs and haplotypes using the transmission disequilibrium test with 148 trios of autistic families. Haplotype G-T-T-T-T-C-G-C in the same eight SNPs was also associated with autism. In summary, our findings provide evidence for a significant association of NRCAM with autism. Considering the important role of the NRCAM gene in brain development, our results therefore indicated that the NRCAM gene is one of the strong candidate genes for autism.

Corresponding author
Address for correspondence: T. Marui, M.D., Ph.D., Department of Neuropsychiatry, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan. Tel.: +81-3-5800-9263Fax: +81-42-379-4544E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

JC Barrett , B Fry , J Maller , MJ Daly (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263265.

E Bonora , JA Lamb , G Barnby , N Sykes , T Moberly , KS Beyer , SM Klauck , F Poustka , E Bacchelli , F Blasi , (2005). Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. European Journal of Human Genetics 13, 198207.

D Clayton , H Jones (1999). Transmission/disequilibrium tests for extended marker haplotypes. American Journal of Human Genetics 65, 11611169.

K Dry , S Kenwrick , A Rosenthal , M Platzer (2001). The complete sequence of the human locus for NgCAM-related cell adhesion molecule reveals a novel alternative exon in chick and man and conserved genomic organization for the L1 subfamily. Gene 273, 115122.

SE Folstein , B Rosen-Sheidley (2001). Genetics of autism: complex aetiology for a heterogeneous disorder. Nature Review Genetics 2, 943955.

SB Gabriel , SF Schaffner , H Nguyen , JM Moore , J Roy , B Blumenstiel , J Higgins , M DeFelice , A Lochner , M Faggart , (2002). The structure of haplotype blocks in the human genome. Science 296, 22252229.

HB Hutcheson , LM Olson , Y Bradford , SE Folstein , SL Santangelo , JS Sutcliffe , JL Haines (2004). Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Medical Genetics [computer file] 5, 12.

RP Lane , XN Chen , K Yamakawa , J Vielmetter , JR Korenberg , WJ Dreyer (1996). Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31. Genomics 35, 456465.

M Lustig , L Erskine , CA Mason , M Grumet , T Sakurai (2001). Nr-CAM expression in the developing mouse nervous system: ventral midline structures, specific fiber tracts, and neuropilar regions. Journal of Comparative Neurology 434, 1328.

M Lustig , T Sakurai , M Grumet (1999). Nr-CAM promotes neurite outgrowth from peripheral ganglia by a mechanism involving axonin-1 as a neuronal receptor. Developmental Biology 209, 340351.

T Marui , I Funatogawa , S Koishi , K Yamamoto , H Matsumoto , O Hashimoto , E Nanba , H Nishida , T Sugiyama , K Kasai , (2007a). Tachykinin 1 (TAC1) gene SNPs and haplotypes with autism: a case-control study. Brain and Development 29, 510513.

T Marui , S Koishi , I Funatogawa , K Yamamoto , H Matsumoto , O Hashimoto , M Ishijima , E Nanba , H Nishida , T Sugiyama , (2007b). No association between the neuronal pentraxin II gene polymorphism and autism. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 940943.

T Marui , S Koishi , I Funatogawa , K Yamamoto , H Matsumoto , O Hashimoto , E Nanba , C Kato , M Ishijima , K Watanabe , (2005). No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population. Neuroscience Research 53, 9194.

M Nothnagel , K Rohde (2005). The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates. American Journal of Human Genetics 77, 988998.

N Risch , D Spiker , L Lotspeich , N Nouri , D Hinds , J Hallmayer , L Kalaydjieva , P McCague , S Dimiceli , T Pitts , (1999). A genomic screen of autism: evidence for a multilocus etiology. American Journal of Human Genetics 65, 493507.

T Sakurai , N Ramoz , JG Reichert , TE Corwin , L Kryzak , CJ Smith , JM Silverman , E Hollander , JD Buxbaum (2006). Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors. Psychiatric Genetics 16, 251257.

S Steffenburg , C Gillberg , L Hellgren , L Andersson , IC Gillberg , G Jakobsson , M Bohman (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry and Allied Disciplines 30, 405416.

P Szatmari , MB Jones , L Zwaigenbaum , JE MacLean (1998). Genetics of autism: overview and new directions. Journal of Autism and Developmental Disorders 28, 351368.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *