The Principles of Clinical Cytogenetics - Extra Materials - Springer

228 Cynthia Powell
Most males with inherited pericentric inversions of the X have a normal phenotype and fertility
(210,215,216). However, X-linked disorders have been found to segregate with pericentric inversions
of the X, presumably by disruption or deletion of a gene by the inversion (217–219). Analysis
of X chromosome inactivation in women with apparently balanced pericentric inversions might determine
whether an imbalance is present at the molecular level. Random inactivation is usually associated
with a balanced inversion, whereas skewed inactivation is more likely associated with an
unbalanced inversion (216,218). Inactivation status of the mother might provide helpful information
in cases of prenatal detection of a male fetus with a maternally inherited inversion (220).
Isodicentric X Chromosomes
Isodicentric X chromosomes are formed by the fusion of two X chromosomes (221). The phenotypic
effects are variable and dependent on whether the chromosomes are fused at long or short arms and
whether there is a deletion. No isochromosome of only the short arm is viable because of the lack of
XIST. Patients with isodicentric X chromosomes joined at their short arms exhibit short or normal
stature, gonadal dysgenesis, and, occasionally, Turner syndrome features, whereas those with long arms
joined are normal or above average in stature and have gonadal dysgenesis (222), normal intelligence,
and no somatic abnormalities (223). Explanations for the phenotype of short stature when the short
arms are joined is most likely secondary to deletion of the distal short arm at the region of SHOX.
Likewise, tall stature could be related to the presence of three copies of SHOX in those patients with
long arms joined.
Mechanisms to explain formation of terminal rearrangements between homologous chromosomes
include the following:
1. Breakage and deletion of a single chromosome followed by rejoining of sister chromatids
2. Breakage and deletion of two homologous chromosomes at the same breakpoints followed by interchromosomal
reunion
3. Terminal fusion without chromatin loss between sister chromatids or homologous chromosomes (224)
The isodicentric X is almost always late-replicating, suggesting nonrandom inactivation of the
derivative X. The second centromere is nonfunctional, making it a pseudodicentric chromosome
(225) (see also the subsection Turner Syndrome, Isochromosome X above).
STRUCTURAL ABNORMALITIES OF THE Y CHROMOSOME
Structural abnormalities of the Y chromosome that lead to deletion of the proximal long arm might
be associated with azoospermia, infertility, and short stature. Marker chromosomes derived from Y
chromosomes are important to detect because of the risk of gonadoblastoma in females with Turner
syndrome. FISH probes have improved the ability to recognize marker Y chromosomes.
Translocations Involving the Y Chromosome
The Y chromosome can be involved in translocations with any other chromosome (another Y, an
X, or an autosome).
(X;Y) Translocations
Hsu reviewed 51 reported cases of (X;Y) translocations, 47 with a derivative X and 4 with a
derivative Y (226). The (X;Y) translocations with a derivative X were divided into seven types, with
the most common types involving translocation of a portion of Yq11.2 → Yqter onto Xp22.3.
Patients with type 1, in which there is a normal Y chromosome and a derivative X with a portion
of Yq translocated to Xp [46,Y,der(X),t(X;Y)(Xqter → Xp22.3::Yq11.2 → Yqter] were phenotypic
males. For those with reported heights (14 of 15 reported), all were short, presumably as a result of
nullisomy for SHOX on Xp22.3. Eleven cases with information available on skin condition showed
evidence of ichthyosis, presumably the result of nullisomy for the steroid sulfatase gene on Xp22. All