2009 Vienna - European Society of Human Genetics

Cytogenetics
ous chromosomal abnormalities; the most part of them have involved
autosomes (eg. trisomy 21, trisomy 18, Cri du Chat syndrome, pericentric
inversion of chromosome 9) while only a few involved sex chromosomes
(eg. Turner syndrome; polisomy X). Several cases have
been diagnosed with various genetic syndromes: Williams syndrome,
DiGeorge syndrome, Cornelia de Lange syndrome, Saethre-Chotzen
syndrome, Klippel Feil syndrome, based on the clinical features. 28
patients with congenital heart diseases and different dysmorphic features
/ developmental delay / multiple congenital anomalies revealed
no numerical or structural chromosomal abnormalities.
Conclusion: Genetic abnormalities are an important cause of congenital
heart disease in children. Cytogenetic analysis should be the first
step in the protocol of investigation in all children with congenital heart
disease and multiple anomalies.
Acknowledgements: The study was realized in the research program
project Mami no 41-042/2007 financed by the Romanian Ministery of
Education, Research and Youth.
P03.123
interstitial de novo deletion, del(4)(p15.2p16.2), indentified in a
case with non-syndromic mental retardation
C. Sorina Mihaela 1 , A. Arghir 1 , D. Le Tessier 2 , M. Budisteanu 3 , A. Lebbar 2 , G.
Cardos 4 , C. Burloiu 3 , A. Coussement 2 , J. Dupont 2 , A. Lungeanu 4 ;
1 „Victor Babes” National Institute of Pathology, Bucharest, Romania, Bucharest,
Romania, 2 APHP, Cochin Hospital, Cytogenetique Laboratory, “Paris Descartes”
University, Paris, France, 3 “Prof. Dr. Alex. Obregia” Clinical Hospital of
Psychiatry, Bucharest, Romania, 4 „Victor Babes” National Institute of Pathology,
Bucharest, Romania.
Interstitial and terminal deletion of chromosome 4p have been previously
described in association with variable phenotypes. The most
well defined condition is Wolf Hirschhorn syndrome (WHS) generated
by 4p16.3 deletions. More proximal deletion, without WHS phenotype,
but associated with varying degrees of mental retardation, were also
reported.
We report on a 2 year-old girl with dysmorphic features (but lacking the
facial characteristics of WHS), moderate mental retardation, spastic
tetraparesis and congenital heart malformation, exhibiting an interstitial
deletion 4p15.2-16.2.
GTG banding, fluorescent in situ hybridization (FISH) and array-based
comparative genomic hybridization (BAC array-CGH) were performed.
Cytogenetic slides were obtained from peripheral blood cultures, by
standard protocols. For FISH investigations painting probes WC4
(Kreatech) and BAC probes (RP11-338K13, RP11-472B18) were
used. BAC array-CGH using CytoChip was applied on DNA extracted
from peripheral blood with Wizard Genomic DNA Purification Kit (Promega).
Classical cytogenetic analysis revealed an interstitial 4p deletion.
Painting probes for chromosome 4 excluded rearragements involving
others chromosomes. BAC array-CGH was applied for a precise delineation
of the deleted region. Proximal and distal breakpoints were
established at 4p15.2 and 4p16.2 respectively. Array-CGH result were
further confirmed by FISH with BAC RP11-338K13 and RP11-472B18
probes. Parental karyotypes were normal.
To our knowledge, an association of the described phenotype and
del(4)(p15.2p16.2) has not been described so far. Our results also
strongly support the need for use of various cytogenetic and advanced
molecular techniques, for a correct phenotype/genotype correlation.
P03.124
Double aneuploidy mosaicism in one Romanian male case
V. N. Plaiasu1 , G. Motei1 , A. Costin1 , D. Ochiana1 , E. Neagu2 , D. Iancu2 , B.
Iancu2 ;
1 2 IOMC Prof.dr.Alfred Rusescu, Bucharest, Romania, National Legal Medicine
Institute Mina Minovici, Bucharest, Romania.
The co-occurrence of two numerical
chromosomal abnormalities in same individual is relatively rare. The
purpose of this communication is to report another case with double
aneuploidy discovered as the result of the evaluation of an infant for
possible Down syndrome.
We present a male neonate, who was born to a 30 year old gravida
two parity one mother, at 36 weeks of gestation, by cesarean section.
The pregnancy was uneventful. At birth, the Apgar score was good.
The patient’s birth weight was 2750g (percentile 10), body length 49cm
(percentile 25). He had a healthy brother.
The baby had typical clinical features of trisomy 21, epispadias and
bilateral syndactily of 4 th -5 th toes. The patient didn’t has conditions like
thyroid, digestive and cardiac congenital disease.
Chromosome study from peripheral lymphocytes using GTG-banding
showed mosaicism 47,XY,+21[70]/48,XXY,+21[30] analyzed in 100
metaphases. Molecular analyses were used to verify the cytogenetic
result. This Down syndrome case with a rare cytogenetic abnormality
as a double aneuploidy demonstrated typical Down syndrome manifestation
along with additional features.
Theories concerning the origin of mixed autosomal-gonosomal trisomies
are also discussed.
P03.125
A de novo double translocations 3;14 and 6;20 in a patient with
mental retardation and microcephaly
B. Aleksiūnienė 1,2 , A. Utkus 1,2 , V. Kučinskas 1,2 ;
1 Department of Human and Medical Genetics Faculty of Medicine, Vilnius, Lithuania,
2 Centre for Medical Genetics at Vilnius University Hospital Santariškių
Klinikos, Vilnius, Lithuania.
The presence of two independent apparently balanced reciprocal
translocations in one person is extremely rare.
Here we report a patient with developmental delay and microcephaly
who was found to have a karyotype with two apparently balanced de
novo reciprocal translocations. Chromosomal rearrangements involving
four chromosomes and four breakpoints. The proband was a 3month-old
male who was the product of the first multiple pregnancy
(twins) of 22-year-old mother and a 28- year-old father. The parents
were healthy and no consanguineous. The patient was referred to clinical
geneticist for developmental retardation when he was 3 months
old. His phenotypic findings included microcephaly, small forehead,
closed fontanelles, relatively log ears.
Blood cultures were harvested by standard methods using thymidine
block to achieve mitotic synchronization. Cytogenetic analysis was
performed from GTG banded metaphases. Chromosomal analysis
of peripheral blood lymphocytes revealed a karyotype of 46,XY,t(3;1
4)(q12;q11.2),t(6;20)(q21?p11.2) in all cells. Cytogenetic study of the
proband’s parents and twin sister showed normal karyotypes.
Developmental delay and microcephaly are probably due to small deletions
or gene disruption at one or more breakpoints.
P03.126
Identification of supernumerary marker chromosome 15
S. Midyan 1 , G. Shakhsuvaryan 1 , B. Sukhudyan 2 , L. Nazaryan 3 , R. S. Moller 4,3 ,
Z. Tumer 5 , N. Tommerup 3 ;
1 Center of Medical Genetics, Yerevan, Armenia, 2 Joint Medical Center and Institute
of Child and Adolescent Health, Yerevan, Armenia, 3 Wilhelm Johannsen
Centre for Functional Genome Research, Institute of Cellular and Molecular
Medicine, University of Copenhagen, Copenhagen, Denmark, 4 Danish Epilepsy
Centre, Dianalund, Denmark, 5 Kennedy Center, Glostrup, Denmark.
Among cases with supernumerary marker chromosomes the majority
represents the derivatives of chromosome 15. More frequently these
derivatives are presented with inv dup (15) that cause the tetrasomy of
15q. Less information is published concerning partial trisomy of 15q.
In this study we report identification of a marker chromosome in a female
patient, who was brought to clinical attention because of epilepsy
at age 8 months. She did not have any other clinical features. Reexamination
at the age of 1.8 years the patient showed psychomotor
retardation. She could not sit and stand without assistance. Apart from
left eye strabismus she did not have substantial dysmorphic characteristics.
Classical cytogenetic analysis revealed presence of a supernumerary
marker chromosome. Due to the clinical presentation the
marker chromosome was suspected to be derived from chromosome
15. WCP-FISH confirmed that the marker chromosome was derived
from chromosome15.
We characterized the marker chromosome further with FISH analysis
using BAC clones mapping to chromosome bands 15q15.2; 15q21.1;
15q21.2. The results suggested that the BAC clone RP11-626N18 was
present on the derivative chromosome, while the BAC clones RP11-
626N18 and RP11-235L4 (mapping to bands 15q21.1 and 15q21.2,
respectively) were deleted. We discuss the symptoms of our case
comparing with other cases with partial trisomy15q to clarify the minimal
region responsible for these symptoms developing.