Autistic disorder associated with a paternally derived unbalanced translocation leading to duplication of chromosome 15pter-q13.2: a case report

David J Wu,N Carolyn Schanen,Marian Sigman,Nicholas J Wang,Naghmeh Dorrani,Dahai Liu,Jennette Driscoll

doi:10.1186/1755-8166-2-27

Abstract

Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34. This case suggests that biallelically expressed genes on proximal 15q contribute to the idic(15) autism phenotype.

Highlights

The association of maternally derived chromosome 15 duplications and autism spectrum disorders (ASD) has been well defined
These studies revealed single hybridization signals on each of the der(15) chromosomes for the probes proximal to BP4 and no signal on the der(15) for probe184n23, which lies distal to BP5 (Figure 3F). These studies confirmed the presence of a non-mosaic translocation chromosome that extended through pDJ204m06 at 15q13.2 (27.8 Mb). This is a unique case of a paternally derived duplication of the chromosome 15pter-q13.2 region that has been associated with ASD
His duplication arises from a 3:1 segregation error of a balanced translocation in the paternal germline

Summary

Background

The association of maternally derived chromosome 15 duplications and autism spectrum disorders (ASD) has been well defined (reviewed in [1]). We describe a case of an autistic boy who is trisomic for 15pter-q13.2 and 9q34.12-qter because of a segregation error leading to transmittance of two copies of a balanced paternal translocation chromosome derived from chromosomes 9 and 15 His behavioral profile overlaps the duplication 15q11.2-q13.2 phenotype including the presence of autism, suggesting that the maternally expressed genes on chromosome 15q are not solely responsible for the ASD phenotype. He is trisomic for distal 9q, neither deletions nor duplications of this region have been associated with autistic symptoms [8,9,10,11]. These studies confirmed the presence of a non-mosaic translocation chromosome that extended through pDJ204m06 at 15q13.2 (27.8 Mb)

Conclusions

Methods