A novel 8.5 MB dup(1)(p34.1p34.3) characterized by FISH in a child presenting with congenital heart defect and dysmorphic features

Abstract

Chromosome duplications involving 1p are rarely reported but are apparently associated with short survival as well as congenital malformations and impaired development. Several 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.

Array‐CGH defined chromosome 1p duplication in a patient with autism spectrum disorder, mild mental deficiency, and minor dysmorphic features

“…Array comparative genomic hybridization (array CGH) has recently lead to the characterization of many novel microdeletion and microduplication syndromes; it has revolutionized the genetic testing available for patients with learning disabilities, who have the “chromosomal phenotype” with dysmorphic features and multiple anomalies [Slavotinek, 2008]. Chromosome duplications involving 1p are rarely reported (fewer than 20 patients in the literature) and a distinct phenotype has yet to be defined; patients appear to have short survival, as well as impaired development and congenital malformations, such as congenital heart defects [Lennon et al, 2006]. Among the reported duplicated 1p cases, the variable phenotypic expressivity likely reflects the variation of the duplicated 1p segments.…”

“…Congenital heart defects, delayed acquisition of motor milestones and of language milestones [Lennon et al, 2006…”