The Principles of Clinical Cytogenetics - Extra Materials - Springer

232 Cynthia Powell
contains two genes whose absence or mutation cause spermatogenic failure (USP9Y and DBY) (242–244).
Complete absence of AZFa is associated with complete absence of germ cells. AZFb (Yq11.23)
contains seven Y genes (CDY2, EIF1AY, PRY, RBMY1, SMCY, TTY5, and TTY6). AZFb absence is
associated with a meiotic maturation arrest; that is, spermatogonia and spermatocytes are present in
the patients’ testis tubules in normal amounts but postmeiotic germ cells are completely absent. AZFc
(Yq11.23) contains seven genes (BPY2, CDY1, CSPG4LY, DAZ, GOLGA2LY, TTY3, and TTY4).
AZFc deletions are associated with variable testicular pathology and occasionally are inherited (most
AZF deletions are de novo). AZFc deletions are the most common chromosome abnormality in men
with azoospermia or severe oligozoospermia and most are de novo (245–247). Polymerase chain
reaction (PCR) techniques are needed to identify various deleted regions (see also Chapter 12).
Short stature in males with Xq deletions might be the result of the loss of the GCY (growth control
gene[s] on the Y chromosome) locus near the pericentromeric region of Yq (248,249). No gene has
yet been identified in this region. Using FISH analysis, Kirsch et al. demonstrated 45,X cell lines in
metaphase preparations from all patients with terminal Yq deletions, suggesting that at least in some
patients, short stature could be explained by mosaicism for a 45,X cell line (249).
Y Isochromosomes
In most cases of isochromosome for Yp or Yq, the abnormal chromosome is dicentric and present
in mosaic fashion, usually with a 45,X cell line (see the section Turner Syndrome Variants above).
Phenotypes are extremely variable because of the level of 45,X mosaicism and tissue distribution for
the abnormal Y chromosome.
i(Yp)
Phenotypic features reported in patients with isochromosome for the short arm of Y include
ambiguous genitalia and Turner syndrome features with normal stature (226,250), although cytogenetic
methods could not rule out a partial Yq deletion (226). Other patients were phenotypic males.
One who was an adult male had hypogonadism, short stature, mental retardation, and facial anomalies
(251). Without a demonstrable 45,X cell line, most cases with monocentric i(Yp) will have a
male phenotype (226).
i(Yq)
Hsu reviewed seven reported cases with nonmosaic, monocentric isochromosome Yq. All were
phenotypic females (expected because of the absence of SRY), with sexual infantilism and streak
gonads. Approximately half had Turner syndrome features and short stature. The lack of Yp in a case
with monocentric i(Yq) without a demonstrable 45,X cell line leads to a female phenotype with
typical or atypical Turner syndrome (226).
Isodicentric Y
The dicentric Y is among the most commonly detected structural abnormalities of the Y chromosome
(see Fig. 8) (226). Most (91%) are found in mosaic form, usually with the other cell line being
45,X. Therefore, it is difficult to know the phenotypic effects of a dicentric Y alone. Some dicentric
Ys have the breakpoint in the long arm, with duplication of the proximal long arm and entire short
arm, whereas others have the break in the short arm, with the proximal short arm and entire long arm
duplicated.
Most reported patients have short stature, and external genitalia could be female, ambiguous, or
male. Gonadoblastoma has been reported in females with a dicentric Y cell line. Males often have
hypospadias. Azoospermia is common in phenotypic males with an isodicentric Y. Again, this has been
proposed to be the result of the loss of the AZF gene (226,252). Mental retardation has been reported in
a few patients, and schizophrenia in two patients (253,254), although there is a bias of ascertainment in
postnatally diagnosed cases and there are very few reports of prenatally diagnosed cases (252).