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Author Notes:

Jennifer G. Mulle

Department of Human Genetics, School of Medicine, Emory University, Whitehead 305M, 615 Michael Street, Atlanta, GA 30322.

jmulle@emory.edu

R.M.P. performed the statistical analysis, produced all figures and tables, and wrote the manuscript. M.Z. performed preliminary data summaries and a literature review. M.M.M. collected the data and helped with data interpretation. M.E.Z. and J.G.M. edited the manuscript and provided guidance on analyzing and interpreting data. J.G.M. was the principal investigator responsible for study direction. All authors participated in commenting on the drafts and have read and approved the final manuscript.

The authors gratefully acknowledge our study population, the 3q29 duplication community, for their participation and commitment to research. The authors also acknowledge the contributions of the members of the Emory 3q29 Project: Hallie Averbach, Emily Black, Gary J. Bassell, T. Lindsey Burrell, Grace Carlock, Tamara Caspary, Joseph F. Cubells, David Cutler, Paul A. Dawson, Michael P. Epstein, Roberto Espana, Michael J. Gambello, Katrina Goines, Henry R. Johnston, Cheryl Klaiman, Sookyong Koh, Elizabeth J. Leslie, Longchuan Li, Bryan Mak, Tamika Malone, Trenell Mosley, Derek Novacek, Ryan Purcell, Timothy Rutkowski, Rossana Sanchez, Celine A. Saulnier, Jason Schroeder, Esra Sefik, Brittney Sholar, Sarah Shultz, Nikisha Sisodiya, Steven Sloan, Elaine F. Walker, Stephen T. Warren, David Weinshenker, and Zhexing Wen.

The authors declare no potential conflict of interest.

Subjects:

Research Funding:

Emory University, Grant/Award Number: Treasure Your Exceptions Project; National Institutes of Health, Grant/Award Numbers: 1R01MH110701-01A1, T32 GM0008490.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • 3q29 duplication
  • autism
  • epilepsy
  • genomic disorder
  • intellectual disability
  • COPY-NUMBER VARIATION
  • CHILD-BEHAVIOR CHECKLIST
  • AUTISM SPECTRUM DISORDER
  • MOLECULAR CHARACTERIZATION
  • DE-NOVO
  • MICRODUPLICATION
  • VARIANTS
  • EPILEPSY
  • INSIGHTS
  • REGION

New phenotypes associated with 3q29 duplication syndrome: Results from the 3q29 registry

Tools:

Journal Title:

AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Volume:

Volume 182, Number 5

Publisher:

, Pages 1152-1166

Type of Work:

Article | Post-print: After Peer Review

Abstract:

3q29 duplication syndrome (3q29dup) is a rare genomic disorder caused by a 1.6 Mb duplication (GRCh38 chr3:195,998,000-197,623,000). Case reports indicate the 3q29dup is likely to be pathogenic, but the full range of manifestations is not well understood. We used the 3q29 registry (https://3q29.com) to ascertain 31 individuals with 3q29dup, the largest cohort ever surveyed in a systematic way. For comparison, we ascertained 117 individuals with the reciprocal 3q29 deletion and 64 typically developing controls. We used a custom medical and demographic questionnaire to assess physical and developmental phenotypes, and two standardized instruments, the Social Responsiveness Scale and Child Behavior Checklist/Adult Behavior Checklist, to assess social disability. Participants with 3q29dup report a high rate of problems in the first year of life (80.6%), including feeding problems (55%), failure to gain weight (42%), hypotonia (39%), and respiratory distress (29%). In early childhood, learning problems (71.0%) and seizures (25.8%) are common. Additionally, the rate of self-reported autism spectrum disorder diagnoses (39%) is substantially elevated compared to the general population, suggesting that the 3q29 duplication may be an autism susceptibility locus. This is the most comprehensive description of 3q29dup to date. Our findings can be used to develop evidence-based strategies for early intervention and management of 3q29dup.

Copyright information:

2020

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