title: Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G1X8. norman.rosenblum@sickkids.ca
authors: Gregory Ryan
authors: GR
authors: Handrigan
authors: David
authors: D
authors: Chitayat
authors: Anath C
authors: AC
authors: Lionel
authors: Maury
authors: M
authors: Pinsk
authors: Andrea K
authors: AK
authors: Vaags
authors: Christian R
authors: CR
authors: Marshall
authors: Sarah
authors: S
authors: Dyack
authors: Luis F
authors: LF
authors: Escobar
authors: Bridget A
authors: BA
authors: Fernandez
authors: Joseph C
authors: JC
authors: Stegman
authors: Jill A
authors: JA
authors: Rosenfeld
authors: Lisa G
authors: LG
authors: Shaffer
authors: McKinsey
authors: M
authors: Goodenberger
authors: Jennelle C
authors: JC
authors: Hodge
authors: Jason E
authors: JE
authors: Cain
authors: Riyana
authors: R
authors: Babul-Hirji
authors: Dimitri J
authors: DJ
authors: Stavropoulos
authors: Verna
authors: V
authors: Yiu
authors: Stephen W
authors: SW
authors: Scherer
authors: Norman D
authors: ND
authors: Rosenblum
mesh_terms: D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D012097:Repressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C492515:ANKRD11 protein, human; D012097:Repressor Proteins