Clinical phenotype of the recurrent 1q21.1 copy-number variant

Raphael Bernier, Kyle J. Steinman, Beau Reilly, Arianne Stevens Wallace, Elliott H. Sherr, Nicholas Pojman, Heather C. Mefford, Jennifer Gerdts, Rachel Earl, Ellen Hanson, Robin P. Goin-Kochel, Leandra Berry, Stephen Kanne, Leeanne Green Snyder, Sarah Spence, Melissa B. Ramocki, David W. Evans, John E. Spiro, Christa L. Martin, David H. LedbetterWendy K. Chung, H. Alupay, B. Aaronson, S. Ackerman, K. Ankenmann, C. Atwell, E. Aylward, A. Beaudet, M. Benedetti, J. Berman, R. Bernier, A. Bibb, L. Blaskey, C. Brewton, R. Buckner, P. Bukshpun, J. Burko, B. Cerban, Q. Chen, M. Cheong, Z. Chu, W. Chung, C. Dale, A. Dempsey, J. Elgin, J. Olson, Y. Evans, W. A. Faucett, G. Fischbach, T. Moss, On behalf of the Simons VIP consortium

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Purpose:To characterize the clinical phenotype of the recurrent copy-number variation (CNV) at 1q21.1, we assessed the psychiatric and medical phenotypes of 1q21.1 deletion and duplication carriers ascertained through clinical genetic testing and family member cascade testing, with particular emphasis on dimensional assessment across multiple functional domains.Methods:Nineteen individuals with 1q21.1 deletion, 19 individuals with the duplication, and 23 familial controls (noncarrier siblings and parents) spanning early childhood through adulthood were evaluated for psychiatric, neurologic, and other medical diagnoses, and their cognitive, adaptive, language, motor, and neurologic domains were also assessed. Twenty-eight individuals with 1q21.1 CNVs (15 deletion, 13 duplication) underwent structural magnetic resonance brain imaging.Results:Probands with 1q21.1 CNVs presented with a range of psychiatric, neurologic, and medical disorders. Deletion and duplication carriers shared several features, including borderline cognitive functioning, impaired fine and gross motor functioning, articulation abnormalities, and hypotonia. Increased frequency of Autism Spectrum Disorder (ASD) diagnosis, increased ASD symptom severity, and increased prevalence of macrocephaly were observed in the duplication relative to deletion carriers, whereas reciprocally increased prevalence of microcephaly was observed in the deletion carriers.Conclusions:Individuals with 1q21.1 deletions or duplications exhibit consistent deficits on motor and cognitive functioning and abnormalities in head circumference.Genet Med 18 4, 341-349.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalGenetics in Medicine
Issue number4
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
This work was supported by two grants from the Simons Foundation (SFARI award 198677 to R.B., E.H., R.G.K., and W.K.C., and SFARI award 312100 to C.L.M., D.H.L.) and a grant from the National Institutes of Health (MH074090 to D.H.L. and C.L.M.). We are grateful to all the families at the participating Simons Variation in Individuals Project (Simons VIP) sites, as well as the Simons VIP working group (Simons VIP consortium, Neuron, 73:1063'1067, 2012).

Publisher Copyright:
© American College of Medical Genetics and Genomics.


  • 1q21.1 deletion
  • 1q21.1 duplication
  • autism spectrum disorder
  • copy-number variation
  • developmental disability


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