Unexpected cryptic chromosomsal complexity: microarray and FISH analysis reveals an interstitial duplication of 5q13 present in a recombinant chromosome arising from a complex paternal chromosome rearrangement involving chromosomes 5, 7 and 12
As part of a CGH microarray study of patients with dysmorphism, developmental delay and apparently balanced chromosome rearrangements, we investigated a 12 year-old boy, diagnosed with hypogonadotropic hypogonadism, and an apparently balanced complex translocation involving chromosomes 5, 7 and 12. His translocation, 46,XY,t(5;7;12)(q33.3;q32;p13.1), was paternally inherited. Array CGH analysis identified a single duplicated clone on chromosome 3 and a duplicated region on chromosome 5 (5q12.3-14.3) spanning 22Mb. The region on chromosome 5 has 8 duplicated clones interspersed with normal and variable copy number regions.
FISH analysis showed that some clones which hybridised as expected to 5q13 and 5q14, also hybridised to 5q33 around the translocation breakpoint in the patient’s der(5), whilst the same clones were absent from 5q13 but present on 5q33 in the father’s der(5). Clones tested in the mother and a normal control had signals only at the expected loci. Re-examination of the karyotypes suggests that the father’s derived chromosome 5 is a more complex rearrangement than previously thought and is slightly different to that seen in his son. Our initial interpretation is that these findings suggest an intrachromosomal insertion in the father, and that the son’s 5q13 duplication has arisen as a result of meiotic recombination.