Molecular characterization of a new patient with a non-recurrent inv dup del 2q and review of the mechanisms for this rearrangement

Am J Med Genet A. 2010 Oct;152A(10):2670-80. doi: 10.1002/ajmg.a.33613.

Abstract

We report on newborn baby with microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet. Cytogenetic studies revealed an inverted duplication with terminal deletion (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism. Microsatellite markers demonstrated that the inv dup del was maternal in origin and intrachromosomal. Intra or interchromosomal rearrangements may cause this aberration either by a U-type exchange (end-to-end fusion), an unequal crossover between inverted repeats (non-allelic homologous recombination: NAHR), or through breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non-homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined the breakpoints and did not detect a single copy region with a size exceeding 12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb, extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non-recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major clinical characteristics associated with this 2q rearrangement overlap with those commonly found in patients with 2q duplication reported in the literature.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Chromosome Banding
  • Chromosome Deletion*
  • Chromosome Inversion*
  • Chromosomes, Human, Pair 2*
  • Comparative Genomic Hybridization
  • Fathers
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Male
  • Mothers
  • Oligonucleotide Array Sequence Analysis
  • Segmental Duplications, Genomic*