2008 Barcelona - European Society of Human Genetics

Cytogenetics
DISCUSSION: In this study, we present that performing tissue cultures and karyotype
analysis approve that PGD is a reliable option for the patients with several indications
to have a non-affected offspring.
P02.168
chromosomal Abnormalities in a Referred Population for
Karyotype, Role of FISH to Refine the Diagnosis
A. K. Kamel, A. M. Mohamed, N. A. Helmy, H. A. Hussein, S. A. Hammad, H. F.
Kayed, M. I. Shehab, A. Gerzawy, M. Eid, H. Afify;
National Research Centre, Cairo, Egypt.
The aim of this study was to evaluate the cytogenetic findings in Egyptian
cases referred for suspected chromosomal anomalies and to clarify
the role of FISH to refine the clinical diagnosis. Cytogenetic study was
performed on 4890 cases referred to Human Cytogenetic Department,
National Research Centre . Referrals were grouped into 20 different
categories of which genetic counseling represented the highest group
19,2% followed by short stature 12 .4%, repeated abortions10 .2%,
MCA/MR 10% Down syndrome 9 .2% . Chromosomal aberrations were
identified in 17.8% of cases, sex chromosome abnormalities represented
22% of the abnormal chromosomes . The most common autosomal
abnormality was Down Syndrome 52% .In structural chromosome
aberrations of autosome, deletion was the most common 6,8% ,
inversion 6% and translocation 5 .2% .Different FISh probes were used
when indicated, It was applied in 10% of referred cases as in cases of
microdeletion syndromes, marker chromosomes, cryptic translocation,
sex chromosomes identification and subtelomeric deletion. Accurate
and refine cytogenetics and molecular cytogenetics diagnosis in our
cases was the corner stone in proper genetic counseling .
P02.169
characterization of rare karyotype anomaly 45,XX,-
21/46,XX,r(21)by comprehensive FISH: mosaic status and
constitution of ring chromosome 21
A. D. Polityko1 , I. Naumchik1 , N. Rumyantseva1 , O. Khurs1 , E. Jaroshevich1 , K.
Mrasek2 , T. Liehr2 ;
1 2 Republican Medical Center “Mother and Child”, Minsk, Belarus, Institute of
Human Genetics and Anthropology, Jena, Germany.
Mosaic combination of monosomy 21 and partial monosomy due to
ring chromosome 21 is a very rare finding in human karyotype. Here
we describe a 2,5 years old female who has been referred to genetic
department because of multiple congenital malformations (microphtalmia,
cataract, corneal opacity, cerebellum abnormality, heart defect
(ASD), craniofacial dysmorphias) and mental/growth retardation . Parents
were young healthy non-consanguineous couple .
Conventional cytogenetic study of affected child revealed diagnosis
45,XX,-21[160]/46,XX,r(21)(p11q22)[160] de novo (parental karyotypes
were normal) . Somatic aberrations of ring chromosome in clone
with r(21) were not found .
Molecular cytogenetic analysis was performed to characterize the constitution
of r(21) . Following probe sets were used for that: subtel 21q
(Abbott/Vysis), BAC 105E1 (21q21 .1), BAC 143N1 (21q21 .3) . Subtelomeric
segment has been deleted by ring chromosome formation, and
finally r(21) was described as ish r(21)(p12q22)(BAC 105E1+, BAC
143N1+, subtel 21q-) .
Possible mechanisms of the mosaic karyotype abnormalities formation,
clinical and cytogenetic aspects of examination of the patient, and
data of the literature are discussed .
[Supported in parts by DAAD 325/2007, DFG WER 17/01/06] .
P02.170
multiple chromosome abnormalities in a case of neuroblastoma
R. Sonar, B. B. Ganguly;
MGM Center for Genetic Research and Diagnosis, New Bombay, India.
Chromosomal abnormalities play pivotal role in the process of malignant
transformation of neural cells which is named as neuroblastoma .
This malignancy has been studied extensively by various techniques
like cytogenetics, flowcytometry, molecular methods, histopatholgy
etc. to identify the genetic markers for their classfication and gather
information on significant prognostication for selection of appropriate
choice of treatment . The most common genetic events associated with
neuroblastoma are loss of heterozygosity (LOH) for the short arm of
the chromosome 1 (1p), over expression of N-myc proto-oncogene,
triploidy or tetraploidy, and defects in expression or function of nerve
growth factor receptor (NGFR) . In our study, chromosomal analysis
was carried out in the bone marrow sample of 4 years old boy following
unstimulated cell culture technique . Conventional G-banding analysis
of 40 cells revealed multiple complex chromosomal rearrangements,
48,XY,t(1;15)(p22;q24),add(6q25),add(7q32)x2,t(11p;?),t(11q23),add
(12q24),t(19q13;?),del(20q13),+mar in 98% cells . In addition one tetraploid
cell was observed . In this case 1(p22) was not deleted but
translocated to chromosome 15(q24) . Presence of t(11q23) suggests
the loss of critical heterozygous region . The above abnormality suggests
advanced stage of the disease and will experience poor prognosis
. However, most of the participating chromosomes and their break
points could not be identified due to limited resolution of the technique.
Hence, it has been understood that cytogenetic study could form the
primary step for understanding the disease and could further guide
for employment of molecular techniques for analysis of amplification
and/or deletion of other genes .
P02.171
Cytogenetic findings in one case of Nijmegen Syndrome
developing Burkitt lymphoma
V. Belengeanu 1 , M. Stoian 1 , N. Andreescu 1 , A. Belengeanu 1 , M. Banateanu 2 ,
E. Ormerod 3 ;
1 University of Medicine and Pharmacy, Timişoara, Romania, 2 II Pediatric Clinic,
Emergency Clinical Hospital, Timişoara, Romania, 3 Department of Medical
Genetics, Ulleval University Hospital, Oslo, Norway.
Here we report an 8 years old girl who had post natal growth deficiency,
microcephaly, facial dysmorphism, partial syndactyly of the second and
third toes, susceptibility to infections, leucocitosis, immunodeficiency,
adenophathy, but no sign of telangiectasia, ataxia and in evolution developed
malignancy (Burkitt lymfoma). The first lymphocytes culture
from this patient was unsuccessful, which is concordant with other reports
from literature. It is known that is difficult to perform cytogenetic
analysis due to the poor proliferation capacity of lymphocytes . From
the first culture, 9 mitosis could be analysed, 6 metaphases had a normal
karyotype while 3 were incomplete . The second culture revealed
16 mitoses, including four incomplete metaphases . Cells rearrangements
of chromosomes were found in 4 metaphases . Chromosomes
anomalies that we found are: isochromosome 11q, int del(7)(q21),
acentric chromosomes and marker chromosome . The images of the
metaphases were sent for reevaluation at Ulleval University Hospital
Oslo, Department of Medical Genetics . By combining clinical manifestations
and laboratory findings including cytogenetic findings and taking
in account the evolution of the patient we sustain the diagnosis of
Nijmegen Breakage Syndrome . At the moment of reporting this case,
the diagnosis of Nijmegen breakage syndrome was confirmed by molecular
analyses . Our patient had developed malignancy in a relative
short period of time after she was first investigated and the prognosis
is estimated to be poor. This is the first case of Nijmegen Breakage
Syndrome reported in Romania .
P02.172
A child with proportional pre- and postnatal growth retardation,
oculocutaneous albinism and normal intelligence with a
15(q26.2-qter) deletion
M. Poot 1 , M. J. Eleveld 1 , R. van ‘t Slot 1 , A. A. Verrijn Stuart 2 , M. M. van Genderen
3 , R. Hochstenbach 1 , F. A. Beemer 1 ;
1 Department of Medical Genetics, Utrecht, The Netherlands, 2 Department of
Pediatric Endocrinology, Utrecht, The Netherlands, 3 Institute for visually handicapped
children Bartimeus, Zeist, The Netherlands.
We report on an 8 ½ years old girl with severe pre- and postnatal
growth retardation, congenital heart malformation, facial asymmetry,
oculocutaneous albinism, and subluxation of the radial heads . Postnatal
growth was severely retarded and proportionate (height -4 .5 SD,
OFC -3SD at 8 years of age) . Her intelligence was in the low normal
range . Extensive endocrinological studies showed a normal growth
hormone response to glucagon, without high growth hormone levels
possibly indicating growth hormone resistance . At 7 years of age oculocutaneous
albinism was diagnosed . The albinotic phenotype was unusual
because, despite clear ocular and systemic features of albinism,
the girl did not have foveal hypoplasia, misrouting, or nystagmus . By
GTG-banding a deletion of band 15q26 was found . Array-CGH, using
a 3783 BAC array, revealed a segmental monosomy of the 15(q26 .2-
>qter) region, which was narrowed down to a 6 .87 Mb deletion by us-