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

Psychiatr Genet. 2008 Jun;18(3):101-9. doi: 10.1097/YPG.0b013e3282f97df7.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autistic Disorder / genetics*
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Chromosome Breakage*
  • Chromosomes, Artificial, Bacterial
  • Chromosomes, Human, Pair 6 / genetics*
  • Chromosomes, Human, Pair 7 / genetics*
  • Cytogenetic Analysis
  • DNA Mutational Analysis
  • Female
  • Gene Dosage
  • Gene Expression Regulation
  • Genome, Human / genetics
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics
  • Translocation, Genetic*

Substances

  • Nerve Tissue Proteins
  • neuronal pentraxin
  • C-Reactive Protein