부산대학교 도서관

We have recently reported the identification of a de novo balanced translocation t5;18q33.1;q12.1 in a boy with autism. Here we discuss the identification of the breakpoints on chromosomes 5 and 18, and subsequent genomic and candidate gene analyses. The 18q breakpoint lies between desmocollin genes DSC1and DSC2. The chromosome 5 breakpoint lies at the 3′ end of the SH3TC2gene and distal to βadrenergic receptor gene ADRB2and serotonin receptor gene HTR4. We hypothesized that the transcription of one or more of these genes is affected by the translocation by position effect. Looking at allelespecific gene expression for the genes at the 5q locus, we were able to determine that ADRB2is expressed from both the normal and derivative alleles. Due to the lack of expression in available tissues or lack of available informative transcribed SNPs, we were unable to exclude the involvement of SH3TC2and HTR4due to position effect. However, we determined that both DSC1and DSC2are only transcribed from the normal chromosome 18 in lymphocytes from the proband. This monoallelic expression of DSC2may put the patient at risk for arrythmogenic right ventricular cardiomyopathy. Desmocollin genes encode celladhesion molecules, and are also highly expressed in brain regions, and thus may also be important for normal neuronal functioning. While a role for SH3TC2, ADRB2, and HTR4as putative candidate genes for autism cannot be discounted, a role for the desmocollin genes at the 18q breakpoint should also be considered. © 2008 WileyLiss, Inc.