2008 Barcelona - European Society of Human Genetics

Cytogenetics
593 kb microdeletion and microduplication in 16p11 .2 found in ~1%
of patients with autism . The recurrent 16p11 .2 rearrangements implicated
in autism likely occur via nonallelic homologous recombination
(NAHR) between directly oriented LCRs . The breakpoints of the
16p11 .2-p12 .1 deletions were mapped to nonhomologous sequences;
however, the deletions were proposed to have arisen via NAHR . We
present a 17-year-old patient with developmental delay, short stature,
skeletal anomalies, and a normal G-banding karyotype and M-FISH .
Using metaphase HR-CGH, we identified a deletion in 16p11.2-p12.1
and verified it by FISH with BAC clones. Whole genome array CGH
with ~385,000 oligonucleotide probes (NimbleGen) defined the deletion
between ~22 .482 .580-29 .342 .610 bp (6 .8 Mb) . Unexpectedly, we
identified a second deletion ~600 kb in size, mapping ~750 kb distal to
the first one. The breakpoints of both deletions map within nonhomologous
sequences; breakpoint junction sequencing is in progress . We
propose that the deletions arose through recently reported Fork Stalling
and Template Switching (FoSTeS) replication-based mechanism
(Lee at al . 2007) rather than NAHR . Phenotype-genotype correlation
with the previously reported cases will be also presented .
P02.043
3 Dimensional imaging in Wolf-Hirschhorn syndrome
P. Hammond 1 , F. Forzano 2 , F. Faraveli 2 , S. Williams 3 , S. T. South 4 , J. C. Carey 4 ,
O. W. J. Quarrell 3 ;
1 Institute of Child Health, London, United Kingdom, 2 Galliera Hospital, Genoa,
Italy, 3 Sheffield Children’s Hospital, Sheffield, United Kingdom, 4 The University
of Utah, Salt Lake City, UT, United States.
Wolf-Hirschhorn syndrome (WHS) has characteristic facial features
resulting from terminal 4p deletions which may be small or large; or
result from unbalanced translocations . Those with small deletions are
less likely to have congenital anomalies . We used 3D imaging and
dense surface modelling to investigate whether facial features correlate
with the aetiology of the 4p deletions .
3D images and routine karyotype results were collected from patients
attending support group meetings . Excluding adults and unusable images,
dense surface models from 76 Caucasian WHS cases (mean
age 7 .7 years, range 1 .4 - 18 .9 years) were compared with 150 controls
(mean age 7 .9 years, range 0 .2 - 20 .4 years) . The WHS cohort
consisted of 19 large deletions (breakpoint proximal to 4p16 .3); 17
small deletions (breakpoint within 4p16 .3); 12 (4;8) translocations; 11
other translocations and 17 unclassified mainly because the breakpoint
was recorded as 4p16 . Pattern recognition algorithms supported
100% discrimination between WHS and control images . Eight additional
cases were tested unseen, 4 interstitial deletions and 4 from
different ethnic backgrounds; all were more similar to the mean of the
WHS cases than the controls .
There was a significant time lag in facial growth in WHS that does
not seem to depend on deletion size . Those with larger deletions had
greater facial dysmorphology and greater facial asymmetry than those
with smaller deletions . There is increasing interest in those few children
with the smallest 4p deletions which define the WHS critical regions
. We suggest 3D imaging is used for objective assessment of
these crucial cases .
P02.044
Wolf-Hirschorn syndrome - case report
T. Marcovici1 , I. Sabau1 , I. Simedrea1 , M. Mihaescu1 , M. Puiu1 , R. Tudorache2 ;
1 2 University of Medicine and Pharmacy, Timisoara, Romania, ”Louis Turcanu”
Children’s Emergency Hospital, Timisoara, Romania.
Wolf-Hirschorn syndrome is a rare disease caused by the partial deletion
of the fourth chromosome’s short arm . Female to male ratio is 2:1 .
Because of the vast range of deleted material (1% to 50%) the effect
on each child varies widely, but the facial appearance is suggestive of
4p- syndrome . No treatment exists for the underlying disorder and the
management is supportive .
We present a nine months old female admitted in our clinic for sistolic
cardiac murmur . A comprehensive medical evaluation was made: prenatal
and birth history, physical, neurologic and genetic examinations,
biologic and imagistic evaluations (cardiac and abdominal ultrasonography,
chest and skull films, brain MRI).
The patient is the second child of a young couple . She was delivered
full term with a weight of 3400g and her development was normal .
By clinical examination we noticed craniofacial dysmorphism: right
parieto-occipital plagiocephaly, downward lips, distinct ,,Greek warrior
helmet” face with broad beaked nose, high frontal hairline, frontal
bossing, hypertelorism; dysmorphic downward ears, bilateral preauricular
tubercles, low occipital hair insertion . Skin dimples on elbows
and left parasternal holosistolic cardiac murmur were present . Imagistic
evaluations show large axial and transverse skull diameters and
normal sized .cerebral ventricles . Small ventricular septal defect with
left-to-right shunt was detected . Serologic tests for TORCH syndrome
and immunoglobulin level were normal . Karyotype analysis noticed deletion
in 4p15-pter region .
Conclusion: Although the patient has no growth problems or physical
disabilities, nor mental retardation, constant cardiologic and neurologic
follow-up care is required .
P02.045
the 4P-syndrome. A case report and literature review
F. Mortezapour 1 , F. Mahjoubi 2 ;
1 Iran blood Transfusion Organization Research Centre (IBTO), Tehran, Iran,
Tehran, Islamic Republic of Iran, 2 Iran blood Transfusion Organization Research
Centre (IBTO), Tehran, Iran & Clinical Genetic Dept. National Institute
for Genetic Engineering and Biotecnology, Tehran, Iran, Tehran, Islamic Republic
of Iran.
Wolf-Hirschhorn syndrome (WHS) is a rare developmental disorder
associated with a deletion of short arm of chromosome 4 . Well-known
features of WHS are typical facial anomalies, midline defects, skeletal
anomalies, prenatal and postnatal growth retardation, hypotonia, mental
retardation, and seizures .
Here we report a new case of WHS who was referred to our clinic for
cytogenetic investigation .
Case Report: The patient was a 9 month old baby boy with developmental
delay, hypotonia, respiratory and heart problem, prominent
eyes and forehead and delayed bone age .
Materials and Methods: Lymphocyte cultures from the patients were
set up in RPMI 1640 medium supplemented with 20% FBS . Cell proliferation
was stimulated with phytohemagglutinin . The cells were harvested
after 72 h culture time . Hypotonic treatment of the cells was
performed in 0.052 M KCL for 10 min at 37c. The cells were fixed in
methanol: glacial acetic (3: 1) overnight, and, after washing in fixative,
were dropped onto clean slides . The slides were G-banded and
analyzed .
Result :GTG banded karyotype revealed a deletion of the distsal part
of 4p (p15 .31-pter) . We describe some of the features of our case and
will compare it with other reported cases .
P02.046
Pure de novo trisomy 4p: About 2 cases
M. Chaabouni1 , L. Kraoua1 , I. Ouertani1 , S. Bouzguenda2 , I. Chelly1 , R. Meddeb1
, L. Ben Jemaa1 , F. Maazoul1 , S. Gaigi2 , H. Chaabouni1 ;
1 2 Department of Hereditary and congenital disorders, Tunis, Tunisia, Department
of Foetopathology, la Rabta, Tunis, Tunisia.
Trisomy 4p is a well-known entity as more than 80 cases have been
published . Most of the reports of trisomy 4p were due to unbalanced
translocations and resulting in associated trisomy or monosomy of
other chromosomes . Cases with pure trisomy 4p are seldom .
We report on two cases of pure trisomy 4p arising de novo in a girl and
a male foetus .
The girl aged 7 years presented with mental retardation, behaviour
troubles, growth retardation, asymmetrical skull, microcephaly, triangular
face, strabismus, bulbous nose, teeth malposition, abnormal
shape of the ears and camptodactyly .
Standard karyotype performed on the patient and her parents showed
a derivative chromosome 14 associated with a whole 4p trisomy: 46,X
X,der(14)t(4;14)(p12;q11 .1)mat .
The second case was a male foetus for who a karyotype was performed
because of an increased nuchal translucency and revealed an
add(4)(qter) .The father has a balanced translocation between the homologous
chromosomes 4, his karyotype was 46,XY,t(4;4)(p12;qter) .
Thus, the foetus’ karyotype was interpreted as: 46,XY,der(4)t(4;4)(p1
2;qter)pat .
Fetopathological examination at 19 weeks of gestation showed slight
dysmorphic features, micrognathia, pointed chin, abnormal shape of
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