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

Cytogenetics
somal sperm and that of apoptotic sperm (p>0.05), suggesting that
there is no relationship between the apoptotic and meiotic mechanisms
in spermatozoa from these patients.
In conclusion, based on the increase in DNA fragmentation and the elevated
rate of unbalanced chromosomal spermatozoa, this study indicates
that these exams should be integrated in the genetic exploration
of male carriers of a structural chromosomal abnormality and used to
predict the outcome of ICSI.
P0325. DNA methylation patterns in human adult and embryonic
metaphase chromosomes: similarities and differences
O. A. Efimova 1 , A. A. Pendina 2 , P. V. Kruglyakov 3 , J. A. Shalygina 1 , T. V.
Kuznetsova 2 , V. S. Baranov 2 ;
1 Saint-Petersburg State University, Saint-Petersburg, Russian Federation,
2 D.O.Ott’s Institute of Obstetrics & Gynecololgy RAMS, Saint-Petersburg, Russian
Federation, 3 Transtechnologies Ltd, Saint-Petersburg, Russian Federation.
DNA methylation plays key role in gene silencing and maintenance of
chromatin structure. In our previous study we have shown band-specific
distribution of 5-methylcytosine-rich DNA in human metaphase
chromosomes from adult and fetal lymphocytes by immunofluorescence
with anti-5-methylcytosine antibodies(Eurogentec). This raised
question about reproducibility of 5-methylcytosine-rich DNA distribution
along chromosomes from other tissues at different developmental
stages. The present research was focused on study of 5-methylcytosine
distribution in metaphase chromosomes from cells of different human
embryonic tissues: liver, lung, brain and cytotrophoblast at 5-12weeks
of gestation, as well as from adult mesenchymal stem cells. Pattern of
5-methylcytosine-rich DNA distribution was similar in all analyzed cell
types: 5-methylcytosine-rich sites corresponded to all T-, majority of
R-bands, to short arms of acrocentrics and heterochromatin of chromosomes
1,9,16. Specificity of signal distribution along chromosomes
allowed identification of specific landmarks for each chromosome pair.
These landmarks could be easily detected in any metaphase. In spite
of overall DNA methylation pattern similarity, local tissue-specific peculiarities
were detected. Heterochromatin of chromosomes 1,9,16 was
hypomethylated in cytotrophoblast, as well as number of other bands,
resulting in decreased overall methylation level, if compared to lymphocyte
chromosomes. Overall decrease in methylation is also typical
for mesenchymal stem cells, whereas chromosomes from embryonic
tissues demonstrated either decreased or increased methylation level
in number of bands. Thus, due to high reproducibility, clearly distinguishable
landmarks and minor tissue-specific differences, we suggested
that distribution of 5-methylcytosine-rich DNA can be considered
as specific banding pattern of human metaphase chromosomes
- MeC-banding. Supported by CRDF&RFBR.
P0326. An unusual transmission of a supernumerary marker
chromosome from a mother to a baby presenting congenital
malformation
H. Akin 1 , A. Alpman 2 , A. Aykut 2 , O. Cogulu 2 , F. Ozkinay 2 ;
1 Ege University Faculty of Medicine, Department of Medical Genetics, İzmir,
Turkey, 2 Ege University Faculty of Medicine, Department of Pediatrics, İzmir,
Turkey.
In humans, the presence of supernumerary chromosomes is an unusual
phenomenon, which is often associated with developmental abnormalities
and malformations. Among supernumerary chromosomes
double minute (dms) are extensively associated with cancer cells.
There are few reports of their presence in the peripheral cells of normal
individuals. Double minutes (dmin) are small chromatin particles that
represent a form of extrachromosomal gene amplification.
We describe a 5-month-old boy who had dysmorphological features
with a karyotype presenting supernumerary marker chromosomes as
minutes and double minutes in a mosaic pattern. There was no history
of any teratogen exposure during the pregnancy. His developmental
milestones were delayed. He was brought to hospital for the first time
at 2 months of age because of dysmorphological features and hypotonia.
He was noted to have depressed nasal root, blue sclera, hypertelorism,
epicanthus, micrognathia, retrognathia, high arched palate,
dysmorphic ears, hypopigmented skin lesion on thoracic wall, umblical
hernia and hypoplastic nails. Laboratory tests including complete blood
count, urinalysis, thyroid function tests were normal. Cranial magnetic
resonance imaging and skeletal X-ray survey were normal. Abdominal
ultrasonography revealed hepatomegaly. Visual Evoked Potentials
10
and Brainstem Auditory Evoked Potentials revealed delayed latencies.
His karyotype revealed 47,XY,dmin+[7]/47,XY,min[2]/46,XY[16].
47,XX,+min[2]/46,XX[18] was detected in his mother’s cytogenetic
analysis. To the best of our knowledge this unusual transmission and
presence of minute and double minute chromosomes have not been
reported in the literature. This unusual existence may contribute to the
literature regarding the possible association between extrachromosomal
gene amplification and congenital abnormalities.
P0327. Xp duplication in two brothers: phenotypic and molecular
cytogenetic characterization
C. A. L. Ruivenkamp 1 , K. B. Hansson 1 , D. A. C. Linders 1 , J. Knijnenburg 2 , K.
Szuhai 2 , P. Helderman 1 ;
1 Dept. of Clinical Genetics, Leiden University Medical Center, Leiden, The
Netherlands, 2 Dept. of Molecular Cell Biology, Leiden University Medical Center,
Leiden, The Netherlands.
Duplications within the short arm of the X-chromosome are rare in
males. Surviving males with Xp duplications are nearly all invariable
mentally retarded. Here we report a detailed characterization of a partial
Xp duplication in two brothers with severe mental impairment.
Conventional chromosome analysis illustrated a structurally abnormal
X chromosome in both brothers. The phenotypically normal mother
carried the same abnormal X chromosome, which is preferentially
inactivated. The sister of the brothers had a normal karyotype. Further
characterization of the aberrant X chromosome by ±1 Mb spaced
large clone insert array-CGH revealed a duplication of approximately
13 Mb with the proximal and distal breakpoints located to Xp21.3
and Xp22.2. The exact karyotype of the brothers was defined as
46,Y,dup(X)(p21.3p22.2).
P0328. Molecular cytogenetic analysis of a de novo interstitial
duplication at 1p36 in a female patient.
M. J. V. Hoffer 1 , C. A. L. Ruivenkamp 1 , M. Kriek 1 , K. B. Hansson 1 , J. M. van de
Kamp 1,2 , A. van Haeringen 1 ;
1 Dept. of Clinical Genetics, Leiden University Medical Center, Leiden, The
Netherlands, 2 Dept. of Clinical Genetics and Anthropogenetics, VU University
Medical Center, Amsterdam, The Netherlands.
Chromosomal imbalances are a frequent cause of mental retardation
and congenital malformations. Although aneuploidy accounts for the
majority of imbalances, structural aberrations contribute to a significant
fraction of recognized chromosomal anomalies.
The female patient reported here was the first child of non-consanguineous
parents. She had a healthy younger brother. The family
history was unremarkable. The patient had congenital bilateral ptosis
and swallowing difficulties, necessitating tube feeding during some
months. Examination at the age of 7 months showed severe ptosis,
epicanthus, telecanthus, strabismus convergens, short upturned nose
and open mouth appearance. Examination at the age of 11,5 years
showed in addition a very narrow palate, bifid uvula, narrow entrance
to the pharynx, dental crowding with braces and micrognatia. She has
a delayed development and mild mental retardation.
Conventional karyotyping based on G-banding revealed a duplication
at the terminal end of the short arm of chromosome 1. Analysis of
parental chromosomes revealed normal karyotypes suggesting a de
novo duplication in our patient. The duplicated region was further characterized
using a 250 k SNP array (Affimetrix). The duplication was 3.3
Mb in size with the breakpoints in band 1p36.33 and 1p36.32. Therefore,
the karyotype was defined as 46,XX,dup(1)(p36.33p36.32).
Although monosomy 1p36 is very common, duplications of 1p36 are
extremely rare. The genotype-phenotype correlation of this case will
contribute to a better understanding of the effect of copy number variation
of genes within the 1p36 region.
P0329. Epigenetic background of chromosomal mosaicism in
human miscarriages
E. N. Tolmacheva, A. A. Kashevarova, I. N. Lebedev;
Research Institute of Medical Genetics, Tomsk, Russian Federation.
Chromosomal mosaicism is a feature of abnormal embryo development.
It results from mitotic non-disjunction in aneuploid or in primary
euploid cells. However, the ratio of both mechanisms as well as inducing
factors of mitotic instability are poorly investigated. It is interesting
that increasing of mosaicism frequency is coincided with the wave of
epigenetic reprogramming. We have suggested that alterations in the