The phenotype of recurrent 10q22q23 deletions and duplications

Bregje W.M. Van Bon, Jorune Balciuniene, Gary Fruhman, Sandesh Chakravarthy Sreenath Nagamani, Diane L. Broome, Elizabeth Cameron, Danielle Martinet, Eliane Roulet, Sebastien Jacquemont, Jacques S. Beckmann, Mira Irons, Lorraine Potocki, Brendan Lee, Sau Wai Cheung, Ankita Patel, Melissa Bellini, Angelo Selicorni, Roberto Ciccone, Margherita Silengo, Annalisa VetroNine V. Knoers, Nicole De Leeuw, Rolph Pfundt, Barry Wolf, Petr Jira, Swaroop Aradhya, Pawel Stankiewicz, Han G. Brunner, Orsetta Zuffardi, Scott B. Selleck, James R. Lupski, Bert B.A. De Vries

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


The genomic architecture of the 10q22q23 region is characterised by two low-copy repeats (LCRs3 and 4), and deletions in this region appear to be rare. We report the clinical and molecular characterisation of eight novel deletions and six duplications within the 10q22.3q23.3 region. Five deletions and three duplications occur between LCRs3 and 4, whereas three deletions and three duplications have unique breakpoints. Most of the individuals with the LCR3-4 deletion had developmental delay, mainly affecting speech. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects and congenital breast aplasia were observed. For congenital breast aplasia, the NRG3 gene, known to be involved in early mammary gland development in mice, is a putative candidate gene. For cardiac defects, BMPR1A and GRID1 are putative candidate genes because of their association with cardiac structure and function. Duplications between LCRs3 and 4 are associated with variable phenotypic penetrance. Probands had speech and/or motor delays and dysmorphisms including a broad forehead, deep-set eyes, upslanting palpebral fissures, a smooth philtrum and a thin upper lip. In conclusion, duplications between LCRs3 and 4 on 10q22.3q23.2 may lead to a distinct facial appearance and delays in speech and motor development. However, the phenotypic spectrum is broad, and duplications have also been found in healthy family members of a proband. Reciprocal deletions lead to speech and language delay, mild facial dysmorphisms and, in some individuals, to cerebellar, breast developmental and cardiac defects.

Original languageEnglish (US)
Pages (from-to)400-408
Number of pages9
JournalEuropean Journal of Human Genetics
Issue number4
StatePublished - Apr 2011


  • 10q22.3q23.2
  • BMPR1A
  • GRID1
  • NRG3
  • PTEN
  • breast development

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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