Identification of a balanced complex chromosomal rearrangement involving chromosomes 3, 18 and 21 with recurrent abortion: case report

Abstract

Background: 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.

Results: 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).

Discussion: 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.

Keywords: Complex chromosomal rearrangements (CCRs); Fluorescence in situ hybridization; Genetic counseling; Recurrent spontaneous abortions.

Figure 1

Identification of a complex translocation involving chromosomes 3, 18 and 21. A: Pedigree of the proband’s family (arrow). B: GTG banded karyotype of the proband showing three derivative chromosomes. C: BAC-probes RP11-379C23 (green) (3q27. 2), RP11-190A24 (21q22.3) (orange) and RP11-89 N1 (red) (18q23) demonstrate a translocation among chromosomes 3, 21 and 18. D: BAC-probes TRP11-7H17 (18q23) (green), BAC-probe RP11-57 F7 (18q22.2) (red) and RP11-89H21(21q11.2) (orange) show the insertion of part of chromosome 18 in derivative chromosome 21.

Figure 2

Theoretical pachytene configuration. Pachytene diagram of the proband (II-3) and segregation mode of her son (III-4). The arrows indicate the direction of separation to each pole.