title: Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder.
abstract: BACKGROUND
  Recurrent microdeletions and microduplications of approximately 555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited.
  
  
  METHODS
  We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features.
  
  
  RESULTS
  Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (non-dysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence.
  
  
  CONCLUSIONS
  The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with non-specific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.
authors.affiliation: Provincial Medical Genetics Program, Health Sciences Center, 300 Prince Philip Drive, St. John's Newfoundland, A1B 3V6, Canada. bfernandez@nl.rogers.com
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Brian
authors.initials: B
authors.lastname: Chung
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.forename: Stephen
authors.initials: S
authors.lastname: Meyn
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
authors.forename: Ann M
authors.initials: AM
authors.lastname: Joseph-George
authors.forename: Sara
authors.initials: S
authors.lastname: Mackay
authors.forename: Kathy
authors.initials: K
authors.lastname: Whitten
authors.forename: Barbara
authors.initials: B
authors.lastname: Noble
authors.forename: Cathy
authors.initials: C
authors.lastname: Vardy
authors.forename: Victoria
authors.initials: V
authors.lastname: Crosbie
authors.forename: Sandra
authors.initials: S
authors.lastname: Luscombe
authors.forename: Eva
authors.initials: E
authors.lastname: Tucker
authors.forename: Lesley
authors.initials: L
authors.lastname: Turner
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D000293:Adolescent; D000328:Adult; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis* / Q000235:genetics*; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D025202:Molecular Diagnostic Techniques; D010375:Pedigree; D010641:Phenotype