Tandem duplication mosaicism: characterization of a mosaic dup(5q) and review

Clin Genet. 2001 Nov;60(5):366-70. doi: 10.1034/j.1399-0004.2001.600508.x.


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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Arrhythmias, Cardiac / congenital
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / genetics*
  • Chromosomes, Human, Pair 5 / genetics*
  • Female
  • Gene Duplication*
  • Humans
  • Infant, Newborn
  • Male
  • Mosaicism / genetics*
  • Mosaicism / physiopathology
  • Pregnancy
  • Prenatal Diagnosis
  • Tandem Repeat Sequences
  • Tetralogy of Fallot / diagnosis
  • Tetralogy of Fallot / genetics*