Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are Likely Mediated by Complex Low-Copy Repeats

Pawel Stankiewicz, Shashikant Kulkarni, Avinash V. Dharmadhikari, Srirangan Sampath, Samarth S. Bhatt, Tamim H. Shaikh, Zhilian Xia, Amber N. Pursley, M. Lance Cooper, Marwan Shinawi, Alex R. Paciorkowski, Dorothy K. Grange, Michael J. Noetzel, Scott Saunders, Paul Simons, Marshall Summar, Brendan Lee, Fernando Scaglia, Florence Fellmann, Danielle MartinetJacques S. Beckmann, Alexander Asamoah, Kathryn Platky, Susan Sparks, Ann S. Martin, Suneeta Madan-Khetarpal, Jacqueline Hoover, Livija Medne, Carsten G. Bonnemann, John B. Moeschler, Stephanie E. Vallee, Sumit Parikh, Polly Irwin, Victoria P. Dalzell, Wendy E. Smith, Valerie C. Banks, David B. Flannery, Carolyn M. Lovell, Gary A. Bellus, Kathryn Golden-Grant, Jerome L. Gorski, Jennifer L. Kussmann, Tracy L. McGregor, Rizwan Hamid, Jean Pfotenhauer, Blake C. Ballif, Chad A. Shaw, Sung Hae L. Kang, Carlos A. Bacino, Ankita Patel, Jill A. Rosenfeld, Sau Wai Cheung, Lisa G. Shaffer

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36 Scopus citations


We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals.We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers. Hum Mutat 33:165-179, 2012.

Original languageEnglish
Pages (from-to)165-179
Number of pages15
JournalHuman mutation
Issue number1
StatePublished - Jan 2012


  • Array CGH
  • Chat
  • Genomic rearrangement
  • Slc18a3


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