2008 Barcelona - European Society of Human Genetics

Cytogenetics
Germany, 3 Instituto Superiore di Sanita, Rome, Italy, 4 Fertility Centre, Hamburg,
Germany, 5 Fundacion Jimenez Diaz, Madrid, Spain, 6 Tampere University Hospital,
Tampere, Finland, 7 Labquality Ltd, Helsinki, Finland.
Cytogenetic tests are undertaken to ascertain a specific syndrome/disorder,
exclude a chromosomal cause for multiple miscarriages, define
gender, or whether a pregnancy is chromosomally abnormal . For most
patients a genetic test is only performed once in a lifetime and it is essential,
therefore, that patients receive an accurate result .
A measure of the accuracy of a diagnostic service can be provided
through External Quality Assessment (EQA), including the new European
EQA scheme, CEQA (Cytogenetic European Quality Assessment)
and the National EQA schemes . CEQA has been piloted for the
last two years supported by the Eurogentest Network of Excellence .
The majority of laboratories participating in these EQA schemes demonstrated
satisfactory EQA performance . However, some laboratories
did not detect the chromosome abnormality and in rare cases even
invented a chromosome abnormality .
An important aspect of cytogenetic analysis is to ascertain the breakpoints
involved in a structural rearrangement . However, marked differences
in breakpoints were allocated by participating laboratories
for the same chromosome abnormality . Information on chromosome
breakpoints may be used to initiate additional genetic tests, to ascertain
whether a child will be affected with a specific syndrome, to identify
a critical region or for gene mapping . This imprecision may have
consequences for the validity of any subsequent investigations . The
EQA process has also identified significant variation in the extent of
interpretation given. Some of the common problems identified through
EQA submissions will be presented .
P02.129
mosaic partial trisomy of chromosome 8 in a dysmorphic
newborn child with multiple anomalies
T. Zoerjanova1 , K. Kuuse2 , T. Ilus2 , R. Zordania1 ;
1 2 Tallinn` Children`s Hospital, Tallinn, Estonia, Department of Genetics, Tartu
University Clinics, United Laboratories, Tartu, Estonia.
We present a case of a dysmorphic newborn girl having congenital
anomalies - polycystic kidneys and agenesis of corpus callosum .
Anamnestically: the patient was born 4G/3P praematurely at 33 . gestation
week . Pregnancy duration and results of antenatal investigations
were abnormal - polyhydramnion and dysplastic kidneys were
diagnosed by ultrasound at 32 gestational week and bone dysplasia
was suspected . Birth anthropometry of the patient (2092g/47 cm; OFC
32 cm) was according to gestational age, due to respiratory failure she
needed artificial ventilation. The patient died at the age of one month.
Phenotype of the patient was dysmorphic:low forehead, enophtalm,
bulbous nose, deformed earlobes, bilateral contractures in III fingers
and congenital anomalies of brain and kidneys
were diagnosed .
Cytogenetical investigations: Rapid chromosomal analysis from peripheral
blood showed mosaic result: 46,XX/47,XX,+mar . Additional
cytogenetical analysis by G-banding and FISH method (Chr .8 Whole
Chromosome Painting Probe, Cytocell) revealed the marker chromosome
to be a derivative chromosome 8:
47,XX,+der(8)(pter→q21).ish der(8)(pter→q21)(wcp8+)[14]/46,XX[6].
The karyotypes of parents were normal .
In conclusion we identified a mosaic partial trisomy of chromosome 8
in a dysmorphic newborn . Discussion of possible etiology and clinical
effect of this cytogenetical result will be presented .
P02.130
De novo cytptic deletion of 2q37 in a child with hypotonia and
congenital heart defect
S. K. Murthy, S. Naveed, E. E. M. Al-Rowaished, S. Mani, S. M. Padariyakam,
P. S. Jacob, M. T. A. Ali;
Molecular Cytogenetic Unit, Genetics Center, DOHMS, P.O.Box 9115, Dubai,
United Arab Emirates.
Unbalanced cryptic chromosomal rearrangement involving the telomeric
region is one of the major causes of complex genetic diseases
resulting in mild to severe clinical conditions .We present here genetic
studies on a one month old female child with hypotonia, poor feeding
and congenital heart defect who was referred for chromosomal
studies . Cytogenetic and FISH studies showed a de novo and unbalanced
cryptic chromosomal rearrangement resulting from a transloca-
tion between chromosomes 2q37.1 and 20p13. The final karyotypic
and FISH results were interpreted as 46,XX,der(2)t(2;20)(q37 .1;p13) .
ish der(2)(2ptel+,2qtel-,20ptel+)dn, leading to trisomy of 20pter and
monosomy of 2qter . Due to the severity of her condition she underwent
cardiac surgery, but failed to survive . More than 60 cases of 2q37
terminal deletion have been reported so far with features ranging from
developmental delay, mental retardation, dysmorphism, autism, cardiac
or renal abnormalities etc . A subset of patients with this distal
deletion, are reported to mimic Albright hereditary Osteodystrophy
(AHO) . Recent array CGH studies by Lukusa et al (2004) correlated
2q37 .3 deletion with autism . Molecular cytogenetic studies using FISH
and array CGH should to be considered for patients presenting with
hypotonia, feeding difficulties and failure to thrive. Literature review
and geneotype-phenotype correlation involving 2q37 microdeletion will
be discussed .
P02.131
the facial dysmorphy in the newly recognised microdeletion
2p15-p16.1 refined to a 570 kb region in 2p15
E. Chabchoub 1 , J. R. Vermeesch 1 , T. de Ravel 1 , P. de Cock 2 , J. P. Fryns 1 ;
1 Centre for Human Genetics - University Hospital Gasthuisberg, Leuven, Belgium,
2 Department of Neuropaediatrics - University Hospital Gasthuisberg,
Leuven, Belgium.
The implementation of new technologies such as array-based comparative
genomic hybridisation (aCGH) in the genetic diagnosis screening
of patients with mental retardation and multiple congenital anomalies
(MR/MCA) enabled the detection of novel subtle chromosomal imbalances,
as well as the refinement of already known chromosomal imbalances
and, in some cases, the identification of the respective genes.
Recently a novel 6 .2 Mb microdeletion involving 2p15-p16 .1 was reported
in two patients with autistic disorder (AD) and MR/MCA with
recognisable dysmorphic features .
While screening for genomic copy number variations with a 1 Mb resolution
bacterial artificial chromosome (BAC) aCGH in patients referred
for the aetiological diagnosis of MR/MCA, a de novo 2p microdeletion
was detected and refined by fluorescence in-situ hybridisation (FISH)
to a 570 kb region in 2p15 in a 16 year-old boy presenting with mild
mental retardation and multiple congenital anomalies with facial dysmorphism,
ecomorphic habitus, kyphoscoliosis and congenital heart
defect. In a first step, Marfan and Williams-Beuren syndromes were
excluded by, respectively, FBN1 gene mutation screening and ELN
gene locus specific FISH probe.
We compare our findings with those already reported and we discuss
the phenotype-genotype correlations .
This report supports the evidence of a newly recognised microdeletion
syndrome involving 2p15-16 .1 . We show that this smallest 570 kb
deletion of 2p15 is most likely responsible for the characteristic facial
dysmorphism in this syndrome .
P02.132
A case of interstitial (4)(31.23q34.2)de novo deletion, detected
by GtG, FisH and m-cGH analyses in a boy referred by a
programme of 22q deletion searching
S. Zajączek 1 , M. Constantinou 2 , E. Grygieńczo - Raźniewska 3 , E. Studniak 3 , E.
Kamińska 4 , E. Gawrych 5 , B. Kałużewski 2 ;
1 Cytogenetics Unit, Szczecin, Poland, 2 Dept. of Medical Genetcs, Medical University,
Lodz, Poland, 3 Cytogenetics Unit, Dept of Genetics and Pathology, Pomeranian
Medical University, Szczecin, Poland, 4 Dept of Paediatrics, Children
Hemathology and Oncology, Pomeranian Medical University, Szczecin, Poland,
5 Dept of Child Surgery, Pomeranian Medical University, Szczecin, Poland.
Terminal deletions of 4q are rarely described (less than 100 cases) and
frequently misdiagnosed at first as “22q deletion suspicion”. We present
a 9 year old boy with global retardation, epilepsy, bilateral lips and
cleft palate, unusual facial appearance, ASD II and some other anomalies
. He was recruited to diagnosis by the 22q deletion searching programme,
but karyotype analyses (lymphocytes, GTG 450 -800 bb .,
RBG, FISH) did not show any anomaly of 22 nd chromosome, but surprisingly
revealed deletion, described at first as 46,XY,del(4)(q34qter).
Karyotypes of both parents were normal . More precise m-CGH analyses
(2,44 OLIGO m-CGH Agilent) showed interstitial 25,6 Mbp deletion,
mapped between loci 178055037 and 152423109 (39 Mbp higher
to telomere) . Final karyotype description was then corrected as follows:
46,XY,del(4)(q31 .23q34 .2) . Possible correlations between ge-