Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia

Daniel Moreno-De-Luca, Jennifer G. Mulle, Erin B. Kaminsky, Stephan J. Sanders, Scott M. Myers, Margaret P. Adam, Amy T. Pakula, Nancy J. Eisenhauer, Kim Uhas, Luann Weik, Lisa Guy, Melanie E. Care, Chantal F. Morel, Charlotte Boni, Bonnie Anne Salbert, Ashadeep Chandrareddy, Laurie A. Demmer, Eva W.C. Chow, Urvashi Surti, Swaroop AradhyaDiane L. Pickering, Denae M. Golden, Warren G. Sanger, Emily Aston, Arthur R. Brothman, Troy J. Gliem, Erik C. Thorland, Todd Ackley, Ram Iyer, Shuwen Huang, John C. Barber, John A. Crolla, Stephen T. Warren, Christa L. Martin, David H. Ledbetter

Research output: Contribution to journalArticlepeer-review

214 Scopus citations


Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10 -5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only.

Original languageEnglish (US)
Pages (from-to)618-630
Number of pages13
JournalAmerican journal of human genetics
Issue number5
StatePublished - Nov 12 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia'. Together they form a unique fingerprint.

Cite this