title: Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism.
abstract: Cytogenetic imbalances are increasingly being realized as causes of autism. Here, we report a de novo translocation between the short arms of chromosomes 15 and 16 in a female with autism, epilepsy, and global developmental delay. FISH analysis identified a cryptic deletion of approximately 160 kb at the boundary of the first exon and first intron of the 1.7 Mb ataxin-2 binding protein-1 (A2BP1) gene, also called FOX1. Quantitative real time PCR (Q-PCR) analysis verified a deletion of exon 1 in the 5' promoter region of the A2BP1 gene. Reverse transcription PCR (qRT-PCR) showed reduced mRNA expression in the individual's lymphocytes, demonstrating the functional consequence of the deletion. A2BP1 codes for a brain-expressed RNA binding or splicing factor. Because of emerging evidence in the role of RNA processing and gene regulation in pervasive developmental disorders, we performed further screening of A2BP1 in additional individuals with autism from the Autism Genetics Resource Exchange (AGRE) collection. Twenty-seven SNPs were genotyped across A2BP1 in 206 parent-child trios and two regions showed association at P < or = 0.008 level. No additional deletions or clear mutations were identified in 88 probands by re-sequencing of all exons and surrounding intronic regions or quantitative PCR (Q-PCR) of exon 1. Although only nominal association was observed, and no obvious causal mutations were identified, these results suggest that A2BP1 may affect susceptibility or cause autism in a subset of patients. Further investigations in a larger sample may provide additional information regarding the involvement of this gene in the autistic phenotype.
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA 30322, USA. clmartin@genetics.emory.edu
authors.forename: Christa Lese
authors.initials: CL
authors.lastname: Martin
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Duvall
authors.forename: Yesim
authors.initials: Y
authors.lastname: Ilkin
authors.forename: Jason S
authors.initials: JS
authors.lastname: Simon
authors.forename: M Gladys
authors.initials: MG
authors.lastname: Arreaza
authors.forename: Kristin
authors.initials: K
authors.lastname: Wilkes
authors.forename: Ana
authors.initials: A
authors.lastname: Alvarez-Retuerto
authors.forename: Amy
authors.initials: A
authors.lastname: Whichello
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Powell
authors.forename: Kathleen
authors.initials: K
authors.lastname: Rao
authors.forename: Edwin
authors.initials: E
authors.lastname: Cook
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15; D002897:Chromosomes, Human, Pair 7; D020732:Cytogenetic Analysis; D004827:Epilepsy / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D020033:Protein Isoforms; C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins