Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21

Holly N. Cukier, Daria Salyakina, Sarah F. Blankstein, Joycelyn L. Robinson, Stephanie Sacharow, Deqiong Ma, Harry H. Wright, Ruth K. Abramson, Ramkumar Menon, Scott M. Williams, Jonathan L. Haines, Michael L. Cuccaro, John R. Gilbert, Margaret A. Pericak-Vance

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Copy number variations (CNVs) play a crucial role in the intricate genetics of autism spectrum disorders. A region on chromosome 15q24 vulnerable to both deletions and duplications has been previously implicated in a range of phenotypes including autism, Asperger's syndrome, delayed development, and mild to severe mental retardation. Prior studies have delineated a minimal critical region of approximately 1.33Mb. In this study, a multiplex autism family was evaluated for CNVs using genotyping data from the Illumina 1M BeadChip and analyzed with the PennCNV algorithm. Variants were then identified that co-segregate with autism features in this family. Here, we report autistic first cousins who carry two microduplications concordant with disease. Both duplications were inherited maternally and found to be identical by descent. The first is an approximately 10,000 base pair microduplication within the minimal region on 15q24 that falls across a single gene, ubiquitin-like 7. This is the smallest duplication in the region to result in a neuropsychiatric disorder, potentially narrowing the critical region for susceptibility to developmental and autism spectrum disorders. The second is a novel, 352kb tandem duplication on 7p21 that replicates part of the neurexophilin 1 and islet cell autoantigen 1 genes. The breakpoint junction falls within the intronic regions of these genes and demonstrates a microhomology of four base pairs. Each of these microduplications may contribute to the complex etiology of autism spectrum disorders.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number4
StatePublished - Jun 2011
Externally publishedYes


  • Autism spectrum disorder (ASD)
  • Copy number variation (CNV)
  • Low-copy repeat (LCR)
  • Non-allelic homologous recombination

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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