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Disease Report for: Neuroligin 4 Autism AUTSX2 Asperger syndrome ASPGX2

Alternative name(s)|Neuroligin 4 Asperger syndrome ASPGX2
Autism, susceptibility to, X-linked 2; AUTSX2
Asperger syndrome, X-linked, susceptibility to, 2
Mutation|12 mutations (e.g. : 445kbdel_human-NLGN4X, G99S_human-NLGN4X, I679V_human-NLGN4Y... more)
OMIM: |300427, 300425, 300495

(from OMIM) In 2 brothers with autism, one with typical autism and the other with Asperger syndrome, Jamain et al. (2003) identified a frameshift mutation (1186T) in the human-NLGN4X gene, resulting in a stop codon at position 396 and premature truncation of the protein before the transmembrane domain. The mutation was present in the mother and absent in an unaffected brother and 350 controls. See other contradictory results Gauthier et al. Vincent et al., but other mutations found Laumonnier et al. Yan et al. Incomplete penetrance suspected for some mutations. Recently new findings support the neuroligin pathway in autism. In particular the R451C mutant mice (R451C_mouse-3neur identical to human mutation R451C_human-NLGN3) showed impaired social interactions but enhanced spatial learning abilities. Tabuchi et al. Comments in Garber et al., Crawley et al. (OMIM 300497 incorporated in 300495)

    Title: An Autism-Associated Mutation Impairs Neuroligin-4 Glycosylation and Enhances Excitatory Synaptic Transmission in Human Neurons
    Cast TP, Boesch DJ, Smyth K, Shaw AE, Ghebrial M, Chanda S
    Ref: Journal of Neuroscience, 41:392, 2021 : PubMed


    Title: Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization
    Kopp N, Amarillo I, Martinez-Agosto J, Quintero-Rivera F
    Ref: American Journal of Medicine Genet A, :e62025, 2020 : PubMed


    Title: A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y
    Nguyen TA, Wu K, Pandey S, Lehr AW, Li Y, Bemben MA, Badger JD, 2nd, Lauzon JL, Wang T and Roche KW <4 more author(s)>
    Ref: Neuron, 106:759, 2020 : PubMed


    Title: Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression
    Ross JL, Bloy L, Roberts TPL, Miller J, Xing C, Silverman LA, Zinn AR
    Ref: American Journal of Medicine Genet B Neuropsychiatr Genet, 180:471, 2019 : PubMed


    Title: Analysis of the genes encoding neuroligins NLGN3 and NLGN4 in Bulgarian patients with autism
    Avdjieva-Tzavella DM, Todorov TP, Todorova AP, Kirov AV, Hadjidekova SP, Rukova BB, Litvinenko IO, Hristova-Naydenova DN, Tincheva RS, Toncheva DI
    Ref: Genet Couns, 23:505, 2012 : PubMed


    Title: Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses
    Berninghausen O, Rahman MA, Silva JP, Davletov B, Hopkins C, Ushkaryov YA
    Ref: Journal of Neurochemistry, 103:1855, 2007 : PubMed


    Title: Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses
    Budreck EC, Scheiffele P
    Ref: European Journal of Neuroscience, 26:1738, 2007 : PubMed


    Title: Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering
    Comoletti D, Grishaev A, Whitten AE, Tsigelny I, Taylor P, Trewhella J
    Ref: Structure, 15:693, 2007 : PubMed


    Title: Neurexin-neuroligin signaling in synapse development
    Craig AM, Kang Y
    Ref: Current Opinion in Neurobiology, 17:43, 2007 : PubMed


    Title: Medicine. Testing hypotheses about autism
    Crawley JN
    Ref: Science, 318:56, 2007 : PubMed


    Title: Neuroscience. Autism's cause may reside in abnormalities at the synapse
    Garber K
    Ref: Science, 317:190, 2007 : PubMed


    Title: Adhesion molecules in the nervous system: structural insights into function and diversity
    Shapiro L, Love J, Colman DR
    Ref: Annual Review of Neuroscience, 30:451, 2007 : PubMed


    Title: A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice
    Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Sudhof TC
    Ref: Science, 318:71, 2007 : PubMed


    Title: Neuroligins 3 and 4X interact with syntrophin-gamma2, and the interactions are affected by autism-related mutations
    Yamakawa H, Oyama S, Mitsuhashi H, Sasagawa N, Uchino S, Kohsaka S, Ishiura S
    Ref: Biochemical & Biophysical Research Communications, 355:41, 2007 : PubMed


    Title: NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population
    Gauthier J, Bonnel A, St-Onge J, Karemera L, Laurent S, Mottron L, Fombonne E, Joober R, Rouleau GA
    Ref: American Journal of Medicine Genet B Neuropsychiatr Genet, 132B:74, 2005 : PubMed


    Title: Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients
    Yan J, Oliveira G, Coutinho A, Yang C, Feng J, Katz C, Sram J, Bockholt A, Jones IR and Sommer SS <3 more author(s)>
    Ref: Mol Psychiatry, 10:329, 2005 : PubMed


    Title: Analysis of four neuroligin genes as candidates for autism
    Ylisaukko-oja T, Rehnstrom K, Auranen M, Vanhala R, Alen R, Kempas E, Ellonen P, Turunen JA, Makkonen I and Jarvela I <4 more author(s)>
    Ref: Eur J Hum Genet, 13:1285, 2005 : PubMed


    Title: X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family
    Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, Ronce N, Lemonnier E and Briault S <9 more author(s)>
    Ref: American Journal of Human Genetics, 74:552, 2004 : PubMed


    Title: Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism?
    Talebizadeh Z, Bittel DC, Veatch OJ, Butler MG, Takahashi TN, Miles JH
    Ref: J Autism Dev Disord, 34:735, 2004 : PubMed


    Title: Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands
    Vincent JB, Kolozsvari D, Roberts WS, Bolton PF, Gurling HM, Scherer SW
    Ref: American Journal of Medicine Genet B Neuropsychiatr Genet, 129B:82, 2004 : PubMed


    Title: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
    Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M and Bourgeron T <1 more author(s)>
    Ref: Nat Genet, 34:27, 2003 : PubMed


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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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