Masked complex chromosome rearrangement in a child thought to have del(8qter) as the sole cytogenetic abnormality

Abstract

Cytogenetic analyses of constitutional diseases have disclosed several chromosomal rearrangements. At the molecular level, these rearrangements often result in the breakage of genes or alteration of genome architecture. Fluorescence in situ hybridization (FISH) and molecular investigations of a patient showing hypotonia and dysmorphic traits revealed a masked complex chromosome abnormality previously detected by G-banding as a simple 8qter deletion. To characterize the genetic rearrangements panels of bacterial artificial chromosomes (BACs) covering 8q24.22→qter were constructed, and short tandem repeats (STRs) were used to refine the localization of the breakpoints and to assess the parental origin of the defect. Chromosome 8 displayed the breakpoint at 8q24.22 and an unexpected distal breakpoint at 8q24.23 resulting in unbalanced translocation of a small 8q genomic region on the chromosome 16qter. The study of the 16qter region revealed that the 16q subtelomere was retained and the translocated material of distal 8q was juxtaposed. Moreover, molecular analyses showed that part of the translocated 8qter segment on der(16) was partially duplicated, inverted and that the rearrangement arose in the paternal meiosis. These findings emphasize the complexity of some only apparently simple chromosomal rearrangements and suggest a subtelomeric FISH approach to enhance diagnostic care when a cytogenetic terminal deletion is found.

Complex human chromosomal and genomic rearrangements

“…Deletions at the breakpoint regions are a common finding, but duplications or inversions are also detected [35,36,40,50]. Importantly, when the resolution of the analysis methods used to analyse CCR increases, the initially identified number of breakpoints tends to increase [40,48,50–54]. This observation suggests that many, and possibly the majority of, CCRs detected to date might actually be more complex than initially thought.…”

A de novo complex chromosome rearrangement involving three chromosomes (2, 13, and 18) in an oligospermic male

“…CCRs are rare events; to our knowledge, 156 cases of CCRs have been reported up to the time of writing (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Despite the fact that there are familial cases reported, most CCRs are de novo.…”