Identification of a balanced complex chromosomal rearrangement involving chromosomes 3, 18 and 21 with recurrent...

Complex chromosome rearrangements (CCRs) are constitutional structural rearrangements involve more than two breakpoints on two or more chromosomes. Balanced CCR carriers are often phenotypically normal but associated with high risk of spontaneous abortion and having abnormal offspring with unbalanced karyotype. Here, we report a new familial case of complex chromosome structural aberrations involving chromosomes 3, 18 and 21 and four breakpoints.

Cytogenetic investigations showed a complex chromosomal chromosome rearrangement involving chromosomes 3, 18 and 21 with four breakpoints. 2 of 4 breakpoints were within the long arm of chromosome 18. Three-color fluorescence in situ hybridization (FISH) confirmed the complexity of the rearrangement and showed the derivative 21 to be composed of 3 distinct segments derived from chromosomes 21, 18, and 3. The karyotype of CCR carrier was determined as 46,XX,t(3;21;18)(3pter → 3q12::18q23 → 18qter;21pter → 21q22.1::18q21.1 → 18q23::3q12 → 3qter; 18pter → 18q21.1::21q22.1 → 21qter).

A new complex balanced CCR was characterized using conventional high resolution banding and molecular cytogenetic analysis. The results provided an explanation of recurrent abortion and abnormal child for balanced CCR carriers. Genetic counselling and prenatal diagnosis for couples with a balanced CCR is necessary since they have a high risk of having a child with unbalanced karyotype. Additional studies to reveal the molecular mechanism of CCRs would help reveal the rule of inherited CCRs in offspring.