title: Tandem duplication mosaicism: characterization of a mosaic dup(5q) and review.
abstract: Mosaicism for tandem duplications is rare. Most patients reported had abnormal phenotypes of varying severity, depending on the chromosomal imbalance involved and the level of mosaicism. Post-zygotic unequal sister-chromatid exchange has been proposed as the main mechanism for tandem duplication mosaicism. However, previous molecular analyses have implicated both meiotic and post-zygotic origins for the duplication. We describe a newborn male who was originally diagnosed in utero with arrhythmia and tetralogy of Fallot. He had multiple dysmorphic features including telecanthus, blepharophimosis, high broad nasal bridge with a square-shaped nose, flat philtrum, thin upper lip, down-turned corners of the mouth, high-arched palate, micrognathia, asymmetric ears, and long, thin fingers and toes. Karyotyping of peripheral blood lymphocytes showed mosaicism for a tandem duplication of part of the long arm of one chromosome 5: mos46,XY,dup(5)(q13q33)[6]/46,XY[45]. Fibroblast cultures had the same mosaic karyotype with a higher frequency of the dup(5) clone: mos46,XY,dup(5)(q13q33)[9]/46,XY[21]. Fluorescence in situ hybridization analysis with a wcp5 confirmed the chromosome 5 origin of the additional material. Parental karyotypes were normal indicating a de novo origin of the dup(5) in the proband. Molecular analyses of chromosome 5 sequence-tagged-site (STS) markers in our family were consistent with a post-zygotic origin for the duplication. Therefore, mosaicism for tandem duplications can arise both through meiotic or mitotic errors, as a result of unequal crossing over or unequal sister-chromatid exchange, respectively. Our review indicates that mosaicism for tandem duplications is likely under-ascertained and that parental karyotyping of probands with non-mosaic tandem duplications should be performed.
authors.affiliation: Department of Pediatrics, University of California San Francisco, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Rauen
authors.forename: S M
authors.initials: SM
authors.lastname: Bitts
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Golabi
authors.forename: P D
authors.initials: PD
authors.lastname: Cotter
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D011296:Prenatal Diagnosis; D020080:Tandem Repeat Sequences; D013771:Tetralogy of Fallot / Q000175:diagnosis / Q000235:genetics*