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Original article
Co-occurrence of recurrent duplications of the DiGeorge syndrome region on both chromosome 22 homologues due to inherited and de novo events
  1. Weimin Bi1,
  2. Frank J Probst1,2,
  3. Joanna Wiszniewska1,
  4. Katie Plunkett1,2,
  5. Erin K Roney1,
  6. Brian S Carter3,
  7. Misti D Williams4,
  8. Pawel Stankiewicz1,
  9. Ankita Patel1,
  10. Cathy A Stevens5,
  11. James R Lupski1,2,6,
  12. Sau Wai Cheung1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  2. 2Texas Children's Hospital, Houston, Texas, USA
  3. 3Division of Neonatology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA
  4. 4Division of Medical Genetics and Genomic Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  5. 5Department of Pediatrics, University of Tennessee College of Medicine, Chattanooga, Tennessee, USA
  6. 6Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr Sau W Cheung, MGL Cytogenetics Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX 77030, USA; scheung{at}


Background Genomic rearrangements usually involve one of the two chromosome homologues. Homozygous microdeletion/duplication is very rare. The chromosome 22q11.2 region is prone to recurrent rearrangements due to the presence of low-copy repeats. A common 3 Mb microdeletion causes the well-characterised DiGeorge syndrome (DGS). The reciprocal duplication is associated with an extremely variable phenotype, ranging from apparently normal to learning disabilities and multiple congenital anomalies.

Methods and results We describe duplications of the DGS region on both homologues in five patients from three families, detected by array CGH and confirmed by both fluorescence in situ hybridisation and single nucleotide polymorphism arrays. The proband in the first family is homozygous for the common duplication; one maternally inherited and the other a de novo duplication that was generated by nonallelic homologous recombination during spermatogenesis. The 22q11.2 duplications in the four individuals from the other two families are recurrent duplications on both homologues, one inherited from the mother and the other from the father. The phenotype in the patients with a 22q11.2 tetrasomy is similar to the features seen in duplication patients, including cognitive deficits and variable congenital defects.

Conclusions Our studies that reveal phenotypic variability in patients with four copies of the 22q11.2 genomic segment, demonstrate that both inherited and de novo events can result in the generation of homozygous duplications, and further document how multiple seemingly rare events can occur in a single individual.

  • Microarray
  • Copy-number
  • Clinical genetics
  • Cytogenetics
  • Diagnostics

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