Characterization of a complex chromosomal rearrangement in a girl with PURA syndrome
Complex chromosomal rearrangements are extremely rare in humans. Most apparently balanced complex chromosomal rearrangements are de novo; they usually are detected in phenotypically normal subjects. Nevertheless, in some cases they are found in patients with multiple congenital abnormalities and neurodevelopmental disorders, which may be due to cryptic genomic imbalance. We report on a case of complex chromosomal rearrangement in a patient with an abnormal phenotype and neurodevelopmental delay. The conventional karyotyping of a child showed an apparently balanced three-way translocation t(4;7;5)(q31;p21;q31)dn. FISH and chromosomal microarray revealed that the rearrangement was far more complex than originally diagnosed, with more breakpoints involving chromosomes and four cryptic microdeletions on chromosomes 4 and 5. One copy number variant indicated microdeletion 5q31.3 syndrome associated with deletion/mutation of the gene PURA. A combination of several different approaches, including GTG, FISH and chromosomal microarrays, was sufficient to determine an unexpected level of complexity and to resolve the nature of the complex chromosomal rearrangement.