Abstract
BackgroundRecombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported.ResultWe describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication.ConclusionOur findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.
Highlights
Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter
Our findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion
Recombinant chromosome 4 syndrome appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions
Summary
Recombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. Breakpoint regions of chromosomal inversions often contain high densities of repetitive DNA sequences, such as Alu and L1 elements, leading to speculation that they could mediate chromosomal rearrangements and serve as hot spots for non-allelic homologous recombination (NAHR) [1]. A chromosome containing a large inverted segment and its normal homolog are predicted to form a homosynaptic inversion loop, which leads to optimal pairing of the matching segment [2]. Any odd number of crossovers within the inversion loop leads to the production of two alternate recombinant chromosomes: in one chromosome the distal part of the short arm is duplicated and the distal part of the long arm is deleted; the opposite occurs in the other chromosome. Two alternative recombinants are theoretically possible among the offspring and generally only one is compatible with life, since, large deletions seem to have a more deleterious effect than large duplications [1,3,6,7]
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