ß 2006 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 140A:1864–1870 (2006) Clinical Report A Novel 8.5 MB dup(1)(p34.1p34.3) Characterized by FISH in a Child Presenting With Congenital Heart Defect and Dysmorphic Features P.A. Lennon, 1 C.F. Boerkoel, 1 K. Plunkett, 1 S. Soukam, 2 S.W. Cheung, 1 and A. Patel 1 * ,{ 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 2 Genzyme Genetics, Los Angeles, California Received 8 February 2006; Accepted 8 June 2006 Chromosome duplications involving 1p are rarely reported but are apparently associated with short survival as well as congenital malformations and impaired development. Sev- eral of these have had congenital heart defects, although too few patients have been reported with similar breakpoints to characterize a syndrome. We present a girl with a novel interstitial duplication in the short arm of chromosome 1 [46,XX,dup(1)(p34.1p34.3)]. She presented with congenital heart defects at 1 month and by 1 year of age manifested delayed acquisition of motor milestones and subsequently of language milestones. By breakpoint-mapping using FISH analysis, we determined that her 1p duplication spans 8.5 megabases. Her 1p duplication is the smallest reported to date to contain 1p34 in patients with congenital heart defect due to abnormalities of heart looping during development. Thus, her 8.5 MB duplication provides a target region to search for a potentially dosage-sensitive gene(s) causing abnormal heart looping when duplicated. Two patients have been reported with duplication including 1p34 but without congenital heart defect, and their duplications span all but the distal approximately 2 MB segment duplicated in our patient. Thus, within our patient’s 8.5 MB target region for a dosage sensitive gene leading to looping abnormalities (and thereby congenital heart defect), the distal 2 MB region might well be the region to begin the search. ß 2006 Wiley-Liss, Inc. Key words: duplication; chromosome 1; congenital heart defect; looping How to cite this article: Lennon PA, Boerkoel CF, Plunkett K, Soukam S, Cheung SW, Patel A. 2006. A novel 8.5 MB dup(1)(p34.1p34.3) characterized by FISH in a child presenting with congenital heart defect and dysmorphic features. Am J Med Genet Part A 140A:1864 – 1870. INTRODUCTION Fewer than 20 patients with duplication within the short arm of chromosome 1 (1p) have been reported, and for most, the duplication resulted in fatal congenital anomalies. The phenotypic features associated with interstitial duplications within 1p include severe intrauterine growth retardation [Dhel- lemmes et al., 1988], ambiguous genitalia [Elejalde et al., 1984], Kabuki Make-Up syndrome-like features [Lo et al., 1998], and sex reversal [Wieacker et al., 1996]; most cases present with multiple congenital anomalies including a congenital heart defect. Among the reported duplicated 1p cases, the variable phenotypic expressivity could reflect the variation in the duplicated 1p segments. In this report, we provide a detailed clinical description of our patient and delineate the breakpoints of her 1p duplication by FISH analysis. We also attempt a genotype/phenotype correlation through compar- ison of our patient with reported patients that had pure or complex duplicated 1p that overlapped the duplication identified in our patient. Clinical Description of the Patient The proposita is a 5-year-old girl; she is the eldest child of a healthy 36-year-old Caucasian mother and a healthy 38-year-old Caucasian father. The parents are unrelated. Both her mother and father were in special education and had cognitive delay. Both paternal grandparents did not finish high school, { Assistant Professor. *Correspondence to: A. Patel, Ph.D., Baylor College of Medicine, 2450 Holcombe Blvd., NAB2015, Houston, TX 77021. E-mail: ankitap@bcm.tmc.edu DOI 10.1002/ajmg.a.31392