An Apparently Balanced Complex Chromosome Rearrangement Involving Seven Breaks and Four Chromosomes in a Healthy Female and Segregation/Recombination in Her Affected Son

Abstract

Duplication of the distal 1q and 4p segments are both characterized by the presence of intellectual disability/neurodevelopmental delay and dysmorphisms. Here, we describe a male with a complex chromosome rearrangement (CCR) presenting with overlapping clinical findings between these 2 syndromes. In order to better characterize this CCR, classical karyotyping, FISH, and chromosomal microarray analysis were performed on material from the patient and his parents, which revealed an unbalanced karyotype with duplications at 1q41q43 and 4p15.2p14 in the proband. The rearrangements, which were derived from a maternal balanced karyotype, included an insertion of a segment from the long to the short arm of chromosome 1, a balanced translocation involving chromosomes 14 and 18, and an insertion of a segment from the short arm of chromosome 4 into the derived chromosome 14. This study aimed to better define the clinical history and prognosis of a patient with this rare category of chromosomal aberration. Our results suggest that the frequency of CCR in the general population may be underestimated; when balanced, they may not have a phenotypic effect. Moreover, they emphasize the need for cytogenetic techniques complementary to chromosomal microarray for proper genetic counseling.

A case of complex balanced chromosomal translocations associated with adverse pregnancy outcomes

“…For example, Sinkar and Devi [ 20 ] reported a boy who inherited a significantly balanced chromosomal translocation from his deaf–mute mother, showing mental impairment and aphasia. However, Campos et al [ 21 ] showed that the frequency of balanced CCR in the population may be underestimated since it may not cause phenotypic effects and may not be detected by the analysis method used. This is similar to the results of the present study.…”

Research Article Characterization of a complex chromosomal rearrangement in a girl with PURA syndrome

“…It has been stated that some apparently balanced translocations are in fact CCRs; some CCRs are more complex than initially expected and could often contain cryptic genomic imbalances (Lee et al, 2010;Guilherme et al, 2013;Campos et al, 2021). Kontodiou et al (2015) agreed that using chromosome banding alone is insufficient to distinguish between a balanced versus an unbalanced CCR.…”