Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region

Justine Coppinger, Donna McDonald-Mcginn, Elaine Zackai, Kate Shane, Joan F. Atkin, Alexander Asamoah, Robert Leland, David D. Weaver, Susan Lansky-Shafer, Karen Schmidt, Heidi Feldman, William Cohen, Judy Phalin, Berkley Powell, Blake C. Ballif, Aaron Theisen, Elizabeth Geiger, Chad Haldeman-Englert, Tamim H. Shaikh, Sulagna SaittaBassem A. Bejjani, Lisa G. Shaffer

Research output: Contribution to journalArticle

52 Scopus citations


Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.

Original languageEnglish (US)
Pages (from-to)1377-1383
Number of pages7
JournalHuman molecular genetics
Issue number8
StatePublished - Apr 20 2009


ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Coppinger, J., McDonald-Mcginn, D., Zackai, E., Shane, K., Atkin, J. F., Asamoah, A., Leland, R., Weaver, D. D., Lansky-Shafer, S., Schmidt, K., Feldman, H., Cohen, W., Phalin, J., Powell, B., Ballif, B. C., Theisen, A., Geiger, E., Haldeman-Englert, C., Shaikh, T. H., ... Shaffer, L. G. (2009). Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. Human molecular genetics, 18(8), 1377-1383.