The Principles of Clinical Cytogenetics - Extra Materials - Springer

196 Kathleen Kaiser-Rogers and Kathleen Rao
Robertsonian translocations containing chromosomes 14 or 15 are involved, because both chromosomes
appear to have imprinted regions. Maternal and paternal UPD for chromosome 15 result in
Prader–Willi syndrome and Angelman syndrome, respectively (135,136). Clinically abnormal offspring
have also been documented in association with paternal and maternal UPD for chromosome
14 (137–141). A single reported case of maternal UPD 14 in a normal individual has created uncertainty
regarding the association between maternal UPD 14 and phenotype (138). Because UPD involving
chromosomes 14 and 15 is associated with an adverse outcome, it has been proposed by the
American College of Medical Genetics that prenatal UPD testing be offered when a fetus carrying a
balanced Robertsonian translocation involving one or both of these chromosomes is ascertained.
Although an abnormal phenotype is not likely to be directly associated with UPD for chromosomes 13,
21, and 22, residual disomy/trisomy mosaicism and recessive disease resulting from reduction to homozygosity
through isodisomy might influence the phenotype of all uniparental disomy offspring (134). These
etiologies for disease should be remembered when dealing with any fetus that carries a balanced Robertsonian
translocation involving these chromosomes, especially if the fetus is clinically abnormal (see Chapter 19).
As discussed in the Introduction, for some types of rearrangements the risk for unbalanced offspring
appears to be significantly higher for a female carrier than a male carrier. This appears to be
the case for nonhomologous Robertsonian translocations involving chromosome 21. In female carriers
of these translocations, an unbalanced karyotype is detected in 13–17% of second trimester pregnancies
(29,142). For male carriers, the same risk appears to be less than 2%. Precisely why male
carriers appear to produce fewer unbalanced offspring than their female counterparts is not known.
However, there is some recent evidence suggesting that female Robertsonian translocation carriers
could produce greater numbers of unbalanced gametes than their male counterparts (143).
JUMPING TRANSLOCATIONS
The term “jumping translocation” refers to dynamic or changing translocations that are rarely
observed in constitutional karyotypes. It is used most often to describe a type of mosaicism in which
a specific donor chromosome segment is translocated to two or more different recipient sites over the
course of multiple mitotic cell divisions (144–150). Jewett et al. have described an individual with
four different cell lines in which long arm material of chromosome 15 was translocated to five different
sites (150). Within the child’s main cell line, the chromosome 15 long arm segment was transferred
to the distal long arm of chromosome 8 and the distal short arm of chromosome 7. In additional
cell lines, this same segment was transferred to the long arm of chromosome 12, the short arm of
chromosome 6, or the short arm of chromosome 8.
In other rare situations, families are described in which translocations involving a common donor
chromosome segment but a different recipient chromosome are observed in parent and child (151,152).
Tomkins, for example, describe a mother and daughter with different, apparently balanced translocations
involving the same short arm segment of chromosome 11 (151). The mother carried an (11;22)
translocation while the daughter carried a similar (11;15) translocation. In families like this, chromosome
“jumping” appears to occur during gametogenesis rather than during mitosis, as described earlier.
The breakpoints observed in jumping translocations frequently involve regions known to contain
repetitive DNA sequences such as telomeres, centromeres, and nucleolar organizers (146,150,152,153).
The location of breaks within these repetitive regions and the suspicion that evolutionary chromosome
rearrangements have distributed inactive forms of these sequences throughout the genome suggest
that recombination between homologous sequences might play a role. For now, however, the
mechanism by which jumping translocations occur is unknown.
INSERTIONS
Insertions are complex three-break rearrangements that involve the excision of a portion of a
chromosome from one site (two breaks) and its insertion into another site (one break). The orienta-