Balanced robertsonian carriers have reproductive diiculties for a number of reasons. Ifthe fused chromosomes are homologous, that is, from the same chromosome pair, the carrier can produce only unbalanced gametes. Each egg or sperm contains either both copies of the translocated chromosome, which would result in trisomy if fertilized, or no copy, which would result in monosomy. If the fused chromosomes are nonhomologous, four of the six possible gametes would be abnormal. he most common robertsonian translocation is der(13; 14) (ql0;ql0), which accounts for up to 20 percent of cases of Patau s) ndrome (p. 257).
These abnormal chromosomes are composed of either two q arms or two p arms of one chromosome fused together.
Isochromosomes are thought to arise when the centromere breaks transversely instead of longitudinally during meiosis II or mitosis. They can also result from a meiotic error in a chromosome with a robertsonian translocation. An isochromosome containing the q arms of an acrocentric chromosome behaves like a homologous robertsonian translocation, and such a carrier can produce only abnormal unbalanced gametes. When an isochromosome involves non acrocentric chromosomes, with p arms containing important genetic material, the fusion and abnormal centromere break results in two isochromosomes. One is composed of both p arms, and one is composed of both q arms. It is likely that one of these isochromosomes would be lost during cell division, resulting in the deletion of all the genes located on the lost arm. Thus, a carrier is usually phenotypically abnormal and produces abnormal gametes. The most common isochromosome involves the long arm of the X chromosome, i(Xq), which is the etiology of 15 percent of cases of T umer syndrome.
When there are two breaks in the same chromosome, and the intervening genetic material is inverted before the breaks are repaired, the result is a chromosomal inversion. Although no genetic material is lost or duplicated, the rearrangement may alter gene function. There are two types-pericentric and paracentric inversions.
PericentricInversion. This results from breaks in both the p and q arms of a chromosome, such that the inverted material includes the centromere (Fig. 13-8). A pericentric inversion causes problems in chromosomal alignment during meiosis and confers signiicant risk for the carrier to produce abnormal gametes and abnormal ofspring. In general, the observed risk of abnormal ofspring in a peri centric inversion carrier is 5 to 10 percent if ascertainment was made after the birth of an abnormal child. But the risk is only 1 to 3 percent if prompted by another indication. An important exception is a pericentric inversion on chromosome 9. his is inv(9)(pllq12), which is a normal variant present in approximately 1 percent of the population.
Paracentric Inversion.If there are two breaks within one arm of a chromosome-either p or q-the inverted material does not include the centromere, and the inversion is paracentric (see Fig. 13-8). he carrier makes either normal balanced gametes or gametes that are so abnormal as to preclude fertilization. Thus, although infertility may be a problem, the risk of having an abnormal ofspring is extremely low.
If there are deletions at each end of the same chromosome, the ends may come together to form a ring chromosome. he telomere regions, which are the ends of a chromosome, contain specialized nucleoprotein complexes that stabilize the chromosome. If just the telomeres are lost, all necessary genetic material is retained, and the carrier is essentially balanced. If a deletion extends more proximally than the telomere, the carrier is likely to be phenotypically abnormal. An example of this is a ring X chromosome, which may result in T umer syndrome.