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Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene
Journal article   Open access   Peer reviewed

Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene

Thomas H Wassink, Joseph Piven, Veronica J Vieland, Laura Jenkins, Rebecca Frantz, Christopher W Bartlett, Rhinda Goedken, Deb Childress, M Anne Spence, Moyra Smith, …
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.136B(1), pp.36-44
07/05/2005
DOI: 10.1002/ajmg.b.30180
PMID: 15892143
url
https://escholarship.org/uc/item/9m33n261View
Open Access

Abstract

Autism is a highly heritable neurodevelopmental syndrome with a complex genetic etiology for which no disease genes have yet been definitively identified. We ascertained three subjects with autism spectrum disorders and chromosome 2q37.3 terminal deletions, and refined the deletion breakpoint regions using polymorphism mapping and fluorescence in situ hybridization (FISH) probes. We then genotyped polymorphic markers downstream from the breakpoint region in a sample of autism affected sibling pair families. Both the chromosomal breakpoints and linkage analyses focused our attention on the gene centaurin gamma-2 (CENTG2), an attractive candidate gene based also on its function and pattern of expression. We therefore assessed CENTG2 for its involvement in autism by (1) screening its exons for variants in 199 autistic and 160 non-autistic individuals, and (2) genotyping and assessing intra-genic polymorphisms for linkage and linkage disequilibrium (LD). The exon screen revealed a Ser --> Gly substitution in one proband, an Arg --> Gly substitution in another, and a number of additional variants unique to the autism families. No unique variants were found in the control subjects. The genotyping produced strong evidence for linkage from two intronic polymorphisms, with a maximum two-point HLOD value of 3.96 and a posterior probability of linkage (PPL) of 51%. These results were contradicted, however, by substantially weaker evidence for linkage from multi-point analyses and by no evidence of LD. We conclude, therefore, that 2q37.3 continues to be a region of interest for autism susceptibility, and that CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism.
 Autistic Disorder - genetics Chromosome Deletion Amino Acid Sequence Genetic Predisposition to Disease - genetics Humans Family Health Genotype Male Lod Score Polymorphism, Genetic Sequence Homology, Amino Acid Chromosomes, Human, Pair 2 - genetics DNA Mutational Analysis Female GTPase-Activating Proteins - genetics Mutation ADP-Ribosylation Factors - genetics Microsatellite Repeats Genetic Linkage Telomere - genetics

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