2009 Vienna - European Society of Human Genetics

Cytogenetics
P03.142
A novel Reciprocal translocation t( X ;7) in a child with
Development Delay
F. Mortezapour, M. Rahnama, F. Nasiri, F. Manoochehri, F. Razazian, M. Zamanian,
F. Mahjoubi;
Iranian blood transfusion organization, Tehran, Islamic Republic of Iran.
Here we report a novel translocation with breakpoints never before
reported. A 5 year old girl was referred to our laboratory because of
developmental delay.
Lymphocyte cultures from the patients were set up in RPMI1640 supplemented
with 20% FBS. High resolution chromosome banding was
performed.
Chromosome study revealed an apparently balanced translocation
between chromosome X and7. The karyotype was accessed as
46,XX,t(X;7)(q13;q32). It is possible that genes disrupted by the translocation
breakpoints contribute the patient’s phenotype.
P03.143
Variegated silencing of a large Xq region in a case of balanced
X;2 translocation
A. Conti, R. Genesio, F. Fabbrini, A. Izzo, V. Ronga, A. Mormile, D. Melis, L.
Nitsch;
University Federico II, Napoli, Italy.
Transcriptional silencing of X chromosome starts in the early embryogenesis
of female mammals and randomly inactivates either the
maternally or the paternally derived X chromosome, which thereafter
shows a late replicating behavior. We studied the X inactivation pattern
in a case of reciprocal balanced translocation: 46,XX,t(X;2)(Xpter-
>Xq23::2q35->2qter;2pter->2q34::Xq24->Xqter)de novo, presenting
with a phenotype suggestive of hypomelanosis of Ito: mild mental retardation,
short stature, obesity, hypo-pigmented cutaneous patches,
facial dysmorphisms, myopia, hemi-hypertrophy of limbs, brachydactily.
CGH by Affymetrix SNP array 6.0 excluded microdeletions, microduplications
and loss of heterozygosity at the breakpoints. Methylation
analysis at the androgen receptor locus showed completely skewed X
inactivation in the proband lymphocytes. BrdU immunostaining assay,
combined with in situ hybridization using whole chromosome 2 painting,
demonstrated that the normal X chromosome was late replicating
in 100% of the metaphases from lymphocytes, thus excluding autosome
inactivation. The same analysis, performed in skin fibroblasts,
showed a late replication also in part of the Xq region translocated to
chromosome 2q, in 60% of the metaphases, suggesting gene silencing
in this region. Analysis of histone H3 lysine methylation confirmed the
partial inactivation of the translocated Xq region in fibroblasts. Quantitative
RT-PCR demonstrated downregulation of some genes mapping
to Xq24qter in the proband fibroblasts.
As the altered phenotype can be ascribed neither to chromosome microdeletions/microduplications
nor to inactivation of the translocated
chromosome 2 region, we hypothesize that a mosaic functional nullisomy
of genes mapping to Xq24qter, through a position-effect variegation
mechanism, might be responsible for the phenotypic anomalies
of the proband.
P03.144
trisomy 8 mosaicism syndrome in 2 children from Bulgaria
B. Radeva, M. Boneva, M. Stancheva;
University Children`s Hospital, Sofia, Bulgaria.
Mosaic Warkany syndrome 2 or Trisomy 8 mosaicism syndrome/
T8mS/ is a rare disorder . Over 75 cases have been reported.The
clinical features are extremely variable.The authors identified 2 clinical
cases with Warkany syndrome 2.
The first clinical case is 9 year`s boy with Gipsy origin , born from third
normal pregnancy.After this pregnancy the mother had 7 miscarriages.
The clinical picture included dysmorphic facies , microretrognathy , microcephaly,
many frenulums of the tongue and alveolar ridge , thoracic
deformity , camptodactily, excavated nails, hypertrichosis , mental retardation
with aggressive and autoaggressive behaviour , recurrent
bronchitis and asthma.The CAT showed internal hydrocephaly.The
chromosome analysis in peripheral venous blood revealed trisomy
8p47, XY+8/46, XY.
The second clinical case is 9 year`s old boy with Bulgarian-Turkish
origin, born from first pregnancy with vacuum extraction.He presented
with mental and speech retardation, dysmorphic facies with strabismus
, ptosis of left eye lid, upturned nose, thick and downturned lower
lip, alopecia areata, low-set ears with incisure of the helix, high palate,
camptodactily and contracture of the fingers, kyphosis, recurrent bronchitis
and asthma in early childhood, vitiligo at 7 year`s old .The EEG
was normal.The CAT showed internal hydrocephaly and agenesia
of corpus callosum.The chromosomal analysis in peripheral venous
blood revealed:47,XY+8/46,XY.Discussion of the possible etiology and
clinical results will be presented.
P03.145
De novo unbalanced translocations: how many of them have a
post-zygotic origin?
M. C. Bonaglia1 , R. Giorda1 , M. Vitaloni2 , R. Ciccone2 , O. Zuffardi3 ;
1 2 IRCCS E. Medea, Bosisio Parini (LC), Italy, Università di Pavia, Pavia, Italy,
3Università di Pavia, P, Italy.
Post-zygotic formation of translocations is considered a rare event in
the absence of mosaicism. We have analyzed with array-CGH and
microsatellites analysis of the trios eighteen de novo unbalanced
translocations. In four cases, we demonstrated that the derivative
chromosome was not deleted as expected but contained a distal deletion
associated to a contiguous inverted duplication (inv-dup-del) on
which the second chromosome segment involved in the translocation
had been transposed. In the remaining thirteen cases the derivative
chromosome was deleted as expected but in three cases the deleted
and duplicated portions have different origin. Altogether, these findings
suggest that at least some de novo unbalanced translocations derive
from a dicentric chromosome. Asymmetric breakage of such a chromosome
would result in the formation of an inv-dup-del chromosome
and a simply deleted one and both can be healed by telomere capture
from another chromosome either with different (50% probability) or the
same (50% probability) parental origin. The dicentric chromosome can
be formed, by NAHR and NHEJ, during gametogenesis or early embryogenesis.
Mosaic situation with two or more cells line with different
derivatives, each one originating from the same chromosome demonstrated
the existence of a dicentric chromosome in the zygote. Its
instability should lead during early embryogenesis to different breakages
leading to different cell lines. The most viable one(s) will survive
to term. This same mechanism of origin has been suggested also in
cases of inv-dup-del ring chromosomes. Our data demonstrate that
some if not all de novo unbalanced translocations have a postzygotic
origin.
P03.146
segmental Uniparental Disomy of short and long arm of
chromosome 18, result of parental inversion of chromosome 18
A. Kariminejad, A. Moshtagh, R. Kariminejad, M. Zanganeh, M. H. Kariminejad;
Kariminejad Najmabadi Pathology and Genetics Center, Tehran, Islamic Republic
of Iran.
Here we report a case of familial pericentric in inversion of chromosome
18, inv(18)(p11.2q21.3). The parents are first cousins and have
identical karyotypes: inv(18)(p11.2q21.3).
Their first child’s chromosomal study revealed 46,XY,rec(18)dup(18q)i
nv(18) (p11.2q21.3). He had mild dysmorphic features, in the absence
of mental and developmental retardation. Prenatal diagnosis was performed
for the second pregnancy.
Chromosomal study revealed 46,XX,rec(18)dup(18q)inv(18)(p11.2q2
1.3), rec(18)dup(18p)inv(18)(p11.2q21.3) detected on normal karyotype.
FISH study using 18q and 18p subtelomeric probes showed
two signals for 18p subtelomeric region on one chromosome 18 and
two signals for 18q subtelomeric region on the other chromosome 18.
Therefore chromosomal findings in karyotype were confirmed and
even though the product is a balanced karyotype, the proband has
uniparental disomy for the 18q21.3◊ region and pter◊p11.2 region. The
fetus was chromosomally balanced yet our concern was the possibility
of imprinted gene or genes in the uniparental disomy segments. To
our knowledge complete uniparental disomy of chromosome 18 has
not previously been reported and there is only one report of segmental
uniparental disomy of chromosome 18. Therefore genetic counseling
was difficult for this couple. The couple decided to keep the child. The
infant was born and is now a 1-year-old apparently healthy girl. This
study supports the lack of association of uniparental disomy for these