The Principles of Clinical Cytogenetics - Extra Materials - Springer

250 Linda Marie Randolph
Fig. 2. An ideogram of the X chromosome with locations of various deletions and the corresponding clinical
characteristics. (From ref. 9; reprinted by permission of the author and of Wiley-Liss, Inc., a subsidiary of John
Wiley Sons, Inc.)
had an abnormal karyotype. One of them was a woman with primary amenorrhea and a 46,XY karyotype.
The other was a woman with secondary amenorrhea and a deletion at Xq26.1. This woman had
a family history of premature ovarian failure, and her mother, who had undergone premature ovarian
failure at 28 years, also had this deletion (8). Figure 2 shows locations of different deletions of the X
chromosome and the associated phenotype (see also Chapter 10).
X Chromosome;Autosome Translocations
In a balanced X;autosome translocation, the normal X is generally inactivated (see Chapter 10). If
the abnormal X were inactivated, autosomal material would be inactivated along with it. Inactivation
of autosome genes would probably be a lethal event.
In an unbalanced X-autosome translocation, the normal X chromosome remains active, whereas
the abnormal X is inactivated in an attempt to compensate for the imbalance.
Translocations involving the X chromosome and an autosome are rare, occurring in 1 in about
30,000 live births (4). This relates, in part, to the fact that all males and half of females with this
finding are infertile. For women, the phenotypic effects depend on the breakpoint and the status of
inactivation of the X chromosomes. If the derivative X is active in all cells and the breakpoint does
not interrupt a functional gene, about half have a normal phenotype and half have ovarian failure. In
general, those with ovarian failure have breakpoints within the Xq13-q26 region.
For women with an active derivative X, when the breakpoints interrupt important genes on either
the X or the autosome, a single gene disorder, such as Duchenne muscular dystrophy, could result.
When the derivative X is active in only a portion of cells, multiple anomalies and mental retardation
usually result.