DIA1R is an X-linked gene related to Deleted In Autism-1

PLoS One. 2011 Jan 17;6(1):e14534. doi: 10.1371/journal.pone.0014534.

Abstract

Background: Autism spectrum disorders (ASDS) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene.

Methodology/principal findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue.

Conclusions/significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics*
  • Adaptor Proteins, Vesicular Transport / physiology
  • Biological Transport
  • Child
  • Child Development Disorders, Pervasive / etiology
  • Child Development Disorders, Pervasive / genetics*
  • Chromosomes, Human, Pair 3
  • Computational Biology
  • Genes, X-Linked*
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Tissue Distribution

Substances

  • Adaptor Proteins, Vesicular Transport
  • DIPK2A protein, human
  • DIPK2B protein, human
  • Membrane Proteins