A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder.
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).
Roohi
Jasmin
J
Department of Genetics, Stony Brook University, Stony Brook, New York, USA.
Tegay
David H
DH
Pomeroy
John C
JC
Burkett
Sandra
S
Stone
Gary
G
Stanyon
Roscoe
R
Hatchwell
Eli
E
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
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C485422:RAB11FIP5 protein, human