European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cytogenetics
and his son carried the same derivative der(3)t(Y;3)(q12;p25.3) leading
to a 3pter deletion of less than 10 Mb.
Familial cases of Y translocation usually concern Y heterochromatin
on acrocentric short arm. Involvement of a non-acrocentric partner has
only been reported once to date.
3p deletion syndrome consists of growth retardation, microcephaly,
facial dysmorphism (ptosis, broad nasal tip, micrognathia), mental
retardation and occasional cardiac malformation, deafness and polydactyly.
Size of deletion and phenotype are variable. Only two familial
cases have been reported. In the present observation, 3p telomeric
region is deleted in both mother and her child while only the child express
clinical features that are not typical for 3p deletion syndrome.
Therefore, it can be questioned whether this deletion really accounts
for the patient’s phenotype. Familial study and precise characterization
of the deletion’s size are in progress to shed light on this issue.
P0428. ZFX gene deletion in mosaic 45,X/46,XY female
V. B. Chernykh, L. F. Kurilo, T. G. Tsvetkova, E. V. Il’ina, A. V. Polyakov;
Research Centre for Medical Genetics of Russian Academy of Medical Sciences,
Moscow, Russian Federation.
X/XY mosaicism is associated with a wide spectrum of clinical phenotypes
varied from females with Ullrich-Turner syndrome (UTS), undervirilized
males with mixed gonadal dysgenesis to normal virilized
infertile males with azoospermia. At this the phenotype effects mainly
depend on a presence of intact SRY gene and correlate with gonadal
X/XY mosaicism.
We have examined patient with UTS. The proband was nine-year female
referred to cytogenetic examination because of virilization. Beside
short stature and clitoral hypertrophy, marked skin dryness was
mentioned in this patient.
Chromosome analysis was performed using standard cytogenetic
techniques with GTG- and CBG- staining. Molecular analysis was carried
out on DNA extracted from peripheral leukocytes. PCR amplifications
for SRY, AMG/AMGL, ZFY/ZFX loci and 21 Y-specific STSs have
been performed.
Cytogenetic examination has found a presence of X/XY mosaicism.
In 4 of 50 analyzed metaphases chromosome analysis has demonstrated
a 45,X karyotype. PCR reactions have revealed a presence of
SRY, AMG, AMGL, ZFY loci, and an absence of ZFX locus. Apparently
patient had an Xp21 microdeletion included the ZFX gene. No Y chromosome
microdeletions were found.
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To our knowledge we have reported the first case of ZFX mutation.
This gene encodes zinc finger protein lies within the critical region for
ovarian failure and escapes X inactivation. Although we have found
that in reported patient the XY cells were prevalent in blood lymphocytes,
gonadal mosaicism may be essentially different. Furthermore, it
is not excluded that ZFX gene loss may dismiss the SRY gene effect
on the gonad differentiation.
P0428a. Novel matUPD15 identification by cytogenetic testing
V. Adir, H. Bar-El, M. Zif, A. Shalaata, Z. U. Borochowitz;
The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center,
Technion-Rappaport Faculty of Medicine, Haifa, Israel.
Prader-Willi Syndrome (PWS) is a multisystemic genetic disorder
characterized by infantile hypotonia, feeding difficulties, distinct dysmorphic
features, hypogonadism, psychomotor retardation and morbid
obesity, with an estimated prevalence of 1 in 15,000 individuals. PWS
is caused by the loss of function of paternal expressed genes within
chromosome 15q11-q13, of which an interstitial deletion is observed
in approximately 75% of the patients while a matUPD15 is noted in
about 20%. The remaining 5% are due to a mutation or a translocation
involving the 15q11-13 region.
Here we report on a newborn male with low-birth weight, severe hypotonia
and poor sucking. Decreased fetal movements were noted during
the 3 rd trimester of pregnancy.
Chromosome analysis revealed normal male karyotype, with 2 identical
marked chromosome 15P + S ++ . Parents’ karyotypes were 46XX
15P + S ++ and 46XY, suggestive of a matUPD mechanism, with partial
isodisomy. The newborn’s FISH analysis (Q-Biogene probe), SNRPN
region/ PML control, was normal. Molecular testing of polymorphic
markers along chromosome 15 revealed a matUPD15, with heteroUPD15
from band q11.2 (D15S128) to band q21.1 (D15S659) and
isoUPD at band q26.1 (D15S652). The cytogenetic results suggest
isoUPD of the 15p arm, formed at the 2 nd meiosis nondisjunction, and
the molecular testing shows a double crossing over event in the 15q
arm. To the best of our knowledge, this is the first report of detection
of UPD15 using standard cytogenetic testing. We suspect that due to
these unique findings, further clinical follow-up of this child may yield
a better understanding of the genotype-phenotype correlation among
PWS cases.