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Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
  1. Gregory Ryan Handrigan1,
  2. David Chitayat2,3,
  3. Anath C Lionel4,5,
  4. Maury Pinsk6,
  5. Andrea K Vaags4,
  6. Christian R Marshall4,5,
  7. Sarah Dyack7,
  8. Luis F Escobar8,
  9. Bridget A Fernandez9,
  10. Joseph C Stegman10,
  11. Jill A Rosenfeld11,
  12. Lisa G Shaffer11,
  13. McKinsey Goodenberger12,
  14. Jennelle C Hodge12,
  15. Jason E Cain13,
  16. Riyana Babul-Hirji2,
  17. Dimitri J Stavropoulos14,15,
  18. Verna Yiu6,
  19. Stephen W Scherer4,5,
  20. Norman D Rosenblum13,14,16,17
  1. 1Undergraduate Medical Education, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  2. 2Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada
  3. 3Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  4. 4Program in Genetics and Genome Biology, The Centre for Applied Genomics, Hospital for Sick Children, Toronto, Ontario
  5. 5Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada
  6. 6Department of Pediatrics, Pediatric Nephrology, University of Alberta, Edmonton, Alberta, Canada
  7. 7Department of Paediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
  8. 8Medical Genetics and Neurodevelopmental Center, Peyton Manning Children's Hospital, Indianapolis, Indiana, USA
  9. 9Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada
  10. 10Developmental and Behavioral Clinic of the Carolinas, Concord, North Carolina, USA
  11. 11Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, USA
  12. 12Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  13. 13Division of Nephrology and Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
  14. 14Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  15. 15Department of Pediatric Laboratory Medicine, Cytogenetics Laboratory, Hospital for Sick Children, Toronto, Ontario, Canada
  16. 16Department of Physiology, University of Toronto, Toronto, Ontario, Canada
  17. 17Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Norman D. Rosenblum, Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G1X8; norman.rosenblum{at}


Background The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent.

Aim To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies.

Methods 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray.

Results Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis.

Conclusions Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.

  • Hydronephrosis
  • Copy-number
  • FBXO31
  • MAP1LC3B

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