title: Analysis of four neuroligin genes as candidates for autism.
abstract: Neuroligins are cell-adhesion molecules located at the postsynaptic side of the synapse. Neuroligins interact with beta-neurexins and this interaction is involved in the formation of functional synapses. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have recently been implicated in pathogenesis of autism. The neuroligin gene family consists of five members (NLGN1 at 3q26, NLGN2 at 17p13, NLGN3 at Xq13, NLGN4 at Xp22, and NLGN4Y at Yq11), of which NLGN1 and NLGN3 are located within the best loci observed in our previous genome-wide scan for autism in the Finnish sample. Here, we report a detailed molecular genetic analysis of NLGN1, NLGN3, NLGN4, and NLNG4Y in the Finnish autism sample. Mutation analysis of 30 probands selected from families producing linkage evidence for Xq13 and/or 3q26 loci revealed several polymorphisms, but none of these seemed to be functional. Family-based association analysis in 100 families with autism spectrum disorders yielded only modest associations at NLGN1 (rs1488545, P=0.002), NLGN3 (DXS7132, P=0.014), and NLGN4 (DXS996, P=0.031). We conclude that neuroligin mutations most probably represent rare causes of autism and that it is unlikely that the allelic variants in these genes would be major risk factors for autism.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland. tero.ylisaukko-oja@ktl.fi
authors.forename: Tero
authors.initials: T
authors.lastname: Ylisaukko-oja
authors.forename: Karola
authors.initials: K
authors.lastname: Rehnström
authors.forename: Mari
authors.initials: M
authors.lastname: Auranen
authors.forename: Raija
authors.initials: R
authors.lastname: Vanhala
authors.forename: Reija
authors.initials: R
authors.lastname: Alen
authors.forename: Elli
authors.initials: E
authors.lastname: Kempas
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Joni A
authors.initials: JA
authors.lastname: Turunen
authors.forename: Ismo
authors.initials: I
authors.lastname: Makkonen
authors.forename: Raili
authors.initials: R
authors.lastname: Riikonen
authors.forename: Taina
authors.initials: T
authors.lastname: Nieminen-von Wendt
authors.forename: Lennart
authors.initials: L
authors.lastname: von Wendt
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D018895:Microsatellite Repeats; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000473:pathology / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers; D008565:Membrane Proteins; C430845:NLGN4X protein, human; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C098004:neuroligin 3