A translocation t(6;7)(p11-p12;q22) associated with autism and mental retardation: localization and identification of candidate genes at the breakpoints.

OBJECTIVES

Our aim is to use information from cytogenetic anomalies to identify candidate genes for autism.

METHODS

We have identified a male patient with mental retardation and autism who has a balanced translocation involving chromosomes 6 and 7, described as t(6;7)(p11-p12;q22). This translocation was inherited from an apparently normal father.

RESULTS

Using fluorescence in situ hybridization, we have localized the breakpoints on both the chromosomes; and using bioinformatic genomic analysis, we have identified a number of potential candidate genes at these loci. These include the neural pentraxin 2 gene, NPTX2, and a novel gene encoding a transmembrane protein, TMEM130, which contains a polycystic kidney domain on 7q22. On 6p12 the breakpoint directly interrupts isoform 2 of the human homologue of the mouse dystonin gene. We also performed a 250 K single nucleotide polymorphism microarray analysis and comparative genomic hybridization using a bacterial artificial chromosome microarray to look for minor genomic deletions or duplications in the proband's DNA. The single nucleotide polymorphism microarray analysis identified a number of copy number variants, remote from the translocation breakpoints, containing potential candidate genes.

CONCLUSION

It is conceivable that one or more of the copy number variant regions or either of the two breakpoint locations and the dystonin gene, in particular, may be a new locus for a form of mental retardation, which may also include autistic features.