Research

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

Blake C Ballif¹ , Aaron Theisen¹ , Justine Coppinger¹ , Gordon C Gowans² , Joseph H Hersh² , Suneeta Madan-Khetarpal³ , Karen R Schmidt³ , Raymond Tervo⁴ , Luis F Escobar⁵ , Christopher A Friedrich⁶ , Marie McDonald⁷ , Lindsey Campbell⁸ , Jeffrey E Ming⁸ , Elaine H Zackai⁸ , Bassem A Bejjani^1,9,10 and Lisa G Shaffer^1,9

¹Signature Genomic Laboratories, LLC, Spokane, WA, USA

²Weisskopf Child Evaluation Center, Department of Pediatrics, University of Louisville, Louisville, KY, USA

³Children's Hospital of Pittsburgh, Pittsburgh, PA, USA

⁴Gillette Children's Specialty Healthcare, St. Paul, MN, USA

⁵St. Vincent Hospital, Indianapolis, IN, USA

⁶Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS, USA

⁷Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA

⁸The Children's Hospital of Philadelphia, Philadelphia, PA, USA

⁹School of Molecular Biosciences, Washington State University, Spokane, WA, USA

¹⁰Sacred Heart Medical Center, Spokane, WA, USA

author email corresponding author email

Molecular Cytogenetics 2008, 1:8doi:10.1186/1755-8166-1-8

Published:	28 April 2008

Abstract

Background

Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.

Results

In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and microcephaly. We also identified 19 individuals with duplications of 3q29, five of which appear to be the reciprocal duplication product of the 3q29 microdeletion and 14 of which flank, span, or partially overlap the common deletion region. The clinical features of individuals with microduplications of 3q29 also varied with few common features. De novo and inherited abnormalities were found in both the microdeletion and microduplication cohorts illustrating the need for parental samples to fully characterize these abnormalities.

Conclusion

Our report demonstrates that array CGH is especially suited to identify chromosome abnormalities with unclear or variable presentations.