ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:601–609 (2008) 3q29 Interstitial Microduplication: A New Syndrome in a Three-Generation Family Emily C. Lisi, 1 Ada Hamosh, 1 Kimberly F. Doheny, 1 Elizabeth Squibb, 2 Barbara Jackson, 2 Rebecca Galczynski, 2 George H. Thomas, 1,2,3 and Denise A.S. Batista 2,3 * 1 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 2 Cytogenetics Laboratory, Kennedy Krieger Institute, Baltimore, Maryland 3 Department of Pathology, Johns Hopkins University, Baltimore, Maryland Received 20 April 2007; Accepted 13 October 2007 Microdeletion and microduplication genetic syndromes are known to be a significant cause of developmental delay and dysmorphology. Utilizing high-resolution chromosome ana- lysis, array CGH and SNP technologies we identified a novel genomic syndrome comprising of an interstitial duplication of approximately 1.61 Mb at the distal end of chromosome 3 band q29. The imbalance was present in five individuals in a three generation family with clinical features including mild to moderate mental retardation and microcephaly. The duplicated segment overlaps with and is the genomic counterpart of the recently described microdeletion of 3q29. Both syndromes are proposed to occur by non- allelic homologous recombination between regions of low copy repeats present around the breakpoints. ß 2008 Wiley-Liss, Inc. Key words: duplication 3q29; array CGH; SNP; mental retardation; microcephaly; deletion 3q29 How to cite this article: Lisi EC, Hamosh A, Doheny KF, Squibb E, Jackson B, Galczynski R, Thomas GH, Batista DAS. 2008. 3q29 interstitial microduplication: A new syndrome in a three-generation family. Am J Med Genet Part A 146A:601 – 609. INTRODUCTION Microdeletion and microduplication syndromes involving many different chromosomal segments are significant factors implicated in mental retarda- tion and dysmorphology. High-resolution chromo- some analysis and fluorescence in situ hybridization (FISH) allowed characterization of a number of syndromes including Prader-Willi/Angelman, velo- cardiofacial syndrome/DiGeorge (VCFS/DGS), Wil- liams and Miller-Dieker syndromes. As detection methods improve and become incorporated into clinical practice, newly recognized and characterized syndromes caused by DNA copy number changes will surely emerge. Current predictions, based on array comparative genomic hybridization (a-CGH), estimate that 10–20% of individuals with mental retardation and dysmorphic features have a chromosomal imbalance [Koolen et al., 2006; Rosenberg et al., 2006]. Recently, six individuals were described with an interstitial deletion of about 1.5 Mb on the terminal band of the long arm of chromosome 3 [Willatt et al., 2005]. These individuals had a variable clinical presentation with mild to moderate mental retarda- tion, microcephaly in two of five patients, growth retardation in three and other minor anomalies. The authors suggested that this deletion at 3q29 was mediated by low copy repeats (LCRs) found within the genomic sequence at each of the breakpoint regions. Meiotic non-allelic homologous recombi- nation between region-specific LCRs can lead to duplication and deletion of the regions involved in these events. There are few reports of patients with isolated 3q29 duplication [Rooms et al., 2006; Rosenberg et al., 2006]. We describe a three generation family with five individuals diagnosed with an interstitial duplication of 3q involving only band q29 detected by high- resolution G-banding. Four of the five individuals are microcephalic and those old enough to test have mild to moderate mental retardation. Utilizing BAC a-CGH, FISH and single nucleotide polymorphism (SNP) analysis we estimated the minimum duplica- tion size to be 1.61 Mb. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www. interscience.wiley.com/jpages/1552-4825/suppmat/index.html. *Correspondence to: Dr. Denise A.S. Batista, Ph.D., Johns Hopkins University, 600 N. Wolfe Street, Cytogenetics Laboratory, Park Bldg, SB 202, Baltimore, MD 21287. E-mail: dbatist1@jhmi.edu DOI 10.1002/ajmg.a.32190