title: A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder.
abstract: Autism spectrum disorder (ASD) is a severe developmental disorder of the central nervous system characterized by impairments in social interaction, communication, and range of interests and behaviors. The syndrome's prevalence is estimated to be as high as 1 in 150 American children yet its etiology remains largely unknown. Examination of observed cytogenetic variants in individuals with ASD may identify genes involved in its pathogenesis. As part of a multidisciplinary study, an apparently balanced de novo translocation between chromosomes 2 and 9 [46,XY,t(2;9)(p13;p24)] was identified in a subject with pervasive developmental disorder not otherwise specified (PDD-NOS), and no distinctive dysmorphic features. Molecular characterization of the rearrangement revealed direct interruption of the RAB11 family interacting protein 5 (RAB11FIP5) gene. RAB11FIP5 is a Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. It is ubiquitously expressed and reported to contribute to both neurotransmitter release and neurotransmitter uptake at the synaptic junction. Detailed analysis of the rearrangement breakpoints suggests that the reciprocal translocation may have formed secondary to incorrect repair of double strand breaks (DSBs) by nonhomologous end-joining (NHEJ).
authors.affiliation: Department of Genetics, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Roohi
authors.forename: David H
authors.initials: DH
authors.lastname: Tegay
authors.forename: John C
authors.initials: JC
authors.lastname: Pomeroy
authors.forename: Sandra
authors.initials: S
authors.lastname: Burkett
authors.forename: Gary
authors.initials: G
authors.lastname: Stone
authors.forename: Roscoe
authors.initials: R
authors.lastname: Stanyon
authors.forename: Eli
authors.initials: E
authors.lastname: Hatchwell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive; D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D015321:Gene Rearrangement; D005820:Genetic Testing; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C485422:RAB11FIP5 protein, human