title: The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system.
abstract: OBJECTIVE
  The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions. To date, the distal 22q11.2 microdeletions have been grouped together as a single clinical entity despite the fact that these deletions are variable in size and position depending on the mediating LCR22s.
  
  
  METHODS
  Here, we report 13 new unrelated patients with variable size deletions in the distal 22q11.2 region as shown by cytogenomic array analyses. We compare our patients' clinical features with those of previously reported cases to better dissect the phenotypic correlations based on the deletion size and position.
  
  
  RESULTS
  Six patients had the 1.1-Mb deletion flanked by LCR22-D and -E, and presented clinically with a phenotype consistent with previously reported cases with distal 22q11.2 microdeletions. Three patients had the 1.8-Mb deletion flanked by LCR22-D and -F, and presented with a similar phenotype. Four patients had the 700-kb deletion flanked by LCR22-E and -F, and presented with a milder phenotype that lacked growth restriction and cardiovascular defects.
  
  
  CONCLUSIONS
  We suggest that the recurrent distal 22q11.2 microdeletions do not represent a single clinical entity, and propose categorizing these deletions into three types according to their genomic position. All three deletion types are thought to be pathogenic and are most often de novo. They all share some presenting features but also have their unique features and risks.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Fady M
authors.initials: FM
authors.lastname: Mikhail
authors.affiliation: Laboratory Corporation of America, Research Triangle Park, North Carolina, USA.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Burnside
authors.affiliation: Laboratory Corporation of America, Research Triangle Park, North Carolina, USA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Rush
authors.affiliation: Department of Pediatrics, Division of Genetics, St. Joseph's Children's Hospital, Paterson, New Jersey, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ibrahim
authors.affiliation: Department of Pediatrics, Division of Genetics, St. Joseph's Children's Hospital, Paterson, New Jersey, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Godshalk
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: S Lane
authors.initials: SL
authors.lastname: Rutledge
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Robin
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Descartes
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult