title: Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism.
abstract: OBJECTIVE
  To screen cDNA for NLGN3 and NLGN4 from lymphoblastoid cells from autistic subjects.
  
  
  RESULTS
  10 young autistic females and 30 non-autistic subjects were studied for alterations in two X linked genes, NLGN3 and NLGN4. A novel NLGN4 isoform lacking exon 4, which occurred de novo on the paternal allele, was identified in one of the autistic females. Monoallelic expression of NLGN4 was seen in this subject and in 11 of 14 informative autistic and non-autistic females using a single nucleotide polymorphism found at 3' UTR. Additionally, the NLGN3 transcript was present in two isoforms (with and without exon 7) in nine of 10 autistic females and in 30 non-autistic subjects, including parents of the autistic female having only the complete transcript with exon 7, and from the whole brain of a control. The novel truncated NLGN3 product may have a regulatory role, as reported in other proteins (for example, vasopressin receptor) by attenuating the function of the full length isoform, resulting in a reduction of the mature protein. Three dimensional protein structures were characterised using comparative modelling, and significant changes were suggested in the protein cores for these two neuroligin isoforms.
  
  
  CONCLUSIONS
  Splice variants may lead to potentially abnormal neuroligins in the causation of autism spectrum disorders.
authors.forename: Z
authors.initials: Z
authors.lastname: Talebizadeh
authors.forename: D Y
authors.initials: DY
authors.lastname: Lam
authors.forename: M F
authors.initials: MF
authors.lastname: Theodoro
authors.forename: D C
authors.initials: DC
authors.lastname: Bittel
authors.forename: G H
authors.initials: GH
authors.lastname: Lushington
authors.forename: M G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D012326:RNA Splicing / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C430845:NLGN4X protein, human; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C098004:neuroligin 3