Interstitial Chromosome 3p13p14 Deletions: An Update and Review

Abstract

Deletions of proximal chromosome 3p13p14 are infrequent chromosomal alterations. Variable sizes and breakpoints have been reported in patients with a wide range of phenotypes that are evolving as additional cases are reported. The routine use of high-density chromosomal microarrays (CMA) has allowed the identification of many more cases of this disorder and clinical phenotyping shows evidence for an emerging profile among patients with overlapping deletions of 3p13p14. Here, we review the currently reported cases, their phenotypes and where available, the genomic intervals delineated by CMA. Surprisingly, we found that a significant number of proximal chromosome 3p deletions involve structural rearrangements, especially insertions, that have been identified in balanced parental chromosome complements. This region is historically known as a common human chromosomal fragile site, although an underlying genomic mechanism related to its architecture has not been identified. We conclude that identification of an interstitial 3p deletion in a proband by CMA should prompt consideration of further structural chromosomal evaluation using more traditional cytogenetic techniques. While the variability in breakpoints does not suggest a unifying underlying mechanism for these alterations, identification of the haploinsufficient genes in each patient's deletion interval and their developmental roles can guide genotype-phenotype correlations and impact clinical management.

Keywords: 3p13p14 deletions; Chromosomal microarray; Structural rearrangements.

Fig. 1

Cases of 3p deletions involving chromosome band 3p13 or 3p14. A total of 30 cases of 3p13 or 3p14 deletions whose array coordinates were published or listed in the DECIPHER database are depicted superimposed on the UCSC genome browser. The coordinates were converted to the Human GRCh37/hg19 assembly from February 2009.