title: Characterization of a de novo translocation t(5;18)(q33.1;q12.1) in an autistic boy identifies a breakpoint close to SH3TC2, ADRB2, and HTR4 on 5q, and within the desmocollin gene cluster on 18q.
abstract: We have recently reported the identification of a de novo balanced translocation t(5;18)(q33.1;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 DSC1 and DSC2. The chromosome 5 breakpoint lies at the 3' end of the SH3TC2 gene and distal to beta-adrenergic receptor gene ADRB2 and 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 allele-specific gene expression for the genes at the 5q locus, we were able to determine that ADRB2 is 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 SH3TC2 and HTR4 due to position effect. However, we determined that both DSC1 and DSC2 are only transcribed from the normal chromosome 18 in lymphocytes from the proband. This monoallelic expression of DSC2 may put the patient at risk for arrythmogenic right ventricular cardiomyopathy. Desmocollin genes encode cell-adhesion 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 HTR4 as putative candidate genes for autism cannot be discounted, a role for the desmocollin genes at the 18q breakpoint should also be considered.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada. john_vincent@camh.net
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Abdul
authors.initials: A
authors.lastname: Noor
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianakopoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzbraun
authors.forename: Simon E
authors.initials: SE
authors.lastname: Alfred
authors.forename: Beata
authors.initials: B
authors.lastname: Stachowiak
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kroisel
authors.forename: Erwin
authors.initials: E
authors.lastname: Petek
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D019457:Chromosome Breakage; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D051187:Desmocollins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C081561:DSC2 protein, human; D051187:Desmocollins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D018343:Receptors, Adrenergic, beta-2; D011985:Receptors, Serotonin; C488620:SH3TC2 protein, human