Molecular analysis of a complex chromosomal rearrangement and a review of familial cases

Abstract

A complex chromosome rearrangement (CCR) involving chromosomes 7, 8, and 13 was detected in a phenotypically normal woman ascertained through her mentally retarded son with abnormal phenotype. He had a karyotype with 47 chromosomes including an extra der(13). In initial banding studies the CCR in the mother was interpreted as a three-way translocation. Fluorescence in situ hybridization with whole chromosome libraries and a telomere-specific probe was used to better characterize the rearrangement. Combined data allowed us to reinterpret the CCR as a translocation and an insertion. A review of 35 familial CCRs involving at least three chromosomes led to the following observations: 1) familial CCRs tend to have fewer chromosomes involved and fewer break-points than do de novo CCRs; 2) familial transmission is mainly observed through female carriers although the origin of de novo cases is paternal; 3) an apparent excess of balanced female carriers among the offspring of index carriers was noted; and 4) meiotic segregation resulting in malformed liveborn infants is most frequently due to adjacent-1 segregation, followed by 4:2 segregation; no adjacent-2 segregation was observed.

Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes

“…In addition, we also should take into consideration the possibilities of 5:3, 6:2, and 7:1 segregation, even if most commonly (78%) abnormal liveborns observed in CCRs are due to adjacent-1 segregation. 3 In conclusion, the calculated probability of normal offspring for the father is very low.…”

“…What is true for inversions, might be also true for CCR: that the longer the inverted segment, the more likely it is that recombination will occur, and that each individual chromosomal inversion carries its own individual risk. Our family is not only extraordinary because of the recombination event in all three 3 A review of 35 familial CCRs led to the following observations. 1.…”

“…Different types of At present at least 114 cases of CCR have been documented. 2 Thirty-five of them were familial cases, reviewed by Batista et al 3 The following conclusions were drawn:…”

Constitutional complex chromosomal rearrangements in a klinefelter patient: case report and review of literature

“…This may be due to severe reproductive impairment through meiotic disturbance or chromosomal imbalance in gametes. Familial transmission has been documented mainly in female [4]. Nevertheless transmission through males has been reported in a few published cases [5].…”

“…Therefore, this is assumed that CCRs may be formed mainly during spermatogenesis but transmitted in families through oogenesis [6]. But very interestingly, the chromosomes involved in CCRs are often preferentially of paternal origin [4].…”