2009 Vienna - European Society of Human Genetics

Cytogenetics
palate, flat broad nose root, loose abdominal muscles. In the USG performed,
no abdominal abnormality and organomegaly were detected.
The karyotype of the case was found to be 46,XX,del (5p) in the chromosome
analysis. 5p- (Cri du Chat) Syndrome is caused by a deletion
on the short arm of chromosome 5 and its incidence ranges between
1:15 000 - 1:50 000 in live births. In the cytogenetic and phenotypic
investigations performed on the short arm of chromosome 5, deletions
in specific size and shape were found to be related to the specific
phenotypic properties. Metaphase plaques obtained from peripheral
blood lymphocytes were investigated and the karyotype of the case
was detected to be 46,XX,del(5p).
P03.161
Identification of Two Novel Cases with Terminal Long Arm
Deletions of chromosome 1 Displaying microcephaly, Epileptic
seizures, corpus callosum Abnormalities
S. Cingöz 1 , S. Hız Kurul 2 , A. Ünalp 3 , U. Yis 2 , Z. Tümer 4 ;
1 Department of Medical Biology and Genetic, School of Medicine, Dokuz Eylül
University, İzmir, Turkey, 2 Department of Pediatrics, Division of Child Neurology,
Dokuz Eylül University School of Medicine, İzmir, Turkey, 3 Department of
Pediatrics, Division of Pediatric Neurology, Behcet Uz Child Disease and Pediatric
Surgery Training and Research Hospital, İzmir, Turkey, 4 Kennedy Center,
Glostrup, Denmark.
Majority of the patients with chromosome 1q terminal deletions have
similar clinical features such as mental retardation, hypotonia, microcephaly,
seizures, corpus callosum abnormalities, congenital cardiac
defects and various facial features.
Here we report two cases with overlapping deletions of the region
1q43-q44 that have been characterized by BAC array CGH (1 Mb
resolution). The first patient had a 6.7-7.9 Mb interstitial deletion at
1q43-q44 chromosomal region. She had mental retardation, developmental
delay, microcephaly, seizure with or without fever and dismorphic
facial features. Magnetic resonance imaging (MRI) investigation
revealed hypoplasia of the corpus callosum. The second patient had
two consecutive interstitial deletions of 2-4 Mb and 4-6.4 Mb, at 1q41
and 1q43-q44, respectively. He had microcephaly, febrile seizures,
ventricular septal defect (VSD), hypospadias, cryptorchidism, and high
palate. MRI investigation revealed dysgenesis of the corpus callosum
and diffuse cerebral atrophy.
In earlier studies, serine/threonine kinase AKT3 gene at 1q44 has
been suggested as a candidate for microcephaly and corpus callosum
agenesis, but was excluded by mapping of the interstitial deletions
involving this region. These studies suggested a new critical region
including four refseq genes, namely C1orf100, ADSS, C1orf101 and
C1orf121 for corpus collosum abnormalities at 1q44. It was deleted in
our two cases. Meanwhile, when we compared the sizes of the deletions
in Patient 2 and previously identified the cases with VSD and
terminal 1q deletion, we refined about a 2Mb new critical region for
VSD associated with 1q43 deletion.
P03.162
A case of de novo pure partial trisomy (6)(p22.3-pter)
J. Tao, X. Ji, W. Jiang, J. Zhang;
Shanghai Institute of Pediatric Research, Shanghai, China.
We report on a 3-year-old girl with psychomotor retardation, speech
development delay, hypothyroidism, and a special pattern of cranofacial
anomalities. Karyotype analysis showed additional material of
unknown origin on the short arm of chromosome 6. Molecular cytogenetic
analysis, by Agilent 44K array CGH, demonstrated a de novo
27.9 Mb duplication from 6p22.3 to 6pter, with no obvious abnormality
on the other chromosomes. Thus, our patient is characterized as being
of pure partial trisomy 6p, which could be distinguished from most
cases found to date. The clinical findings in this patient were compared
to those in the previously reported cases. Genotype-phenotype correlation
suggests further splitting in the partial 6p trisomy syndrome.
The distinct facial features including prominent forehead, blepharophimosis,
blepharoptosis, bulbous nose and small pointed chin, are consistently
recognizable in distal 6p duplication, while severer symptoms
such as feeding problems, recurrent respiratory infections, gastrointestinal
anomalies, limb deformities are more likely associated with
proximal 6p duplication.
P03.163
cri du chat syndrome - clinical and genetic study of a particular
case
R. M. Popescu 1 , C. Rusu 1 , I. Ivanov 2 , M. Covic 1 ;
1 University of Medicine and Pharmacy- Department of Medical Genetics, Iasi,
Romania., Iasi, Romania, 2 Sf Spiridon Hospital Iasi – Immunology and Genetics
Laboratory, Iasi, Romania, Iasi, Romania.
Cri-du-chat syndrome is a genetic disease resulting from a deletion
of variable size occurring on the short arm of chromosome 5. Main
clinical features are: high-pitched monochromatic cry, microcephaly,
broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics
and severe psychomotor and mental retardation. Cardiac,
neurological and renal abnormalities may be associated.
We present a case of a 6 years old patient with “cri-du-chat” syndrome
and complex abnormalities of the karyotype in order to illustrate a rare
form of the disorder and to discuss the management of the patient and
her family.
Anamnestic data show that the girl is the second child born to a young,
unrelated, apparently healthy couple. Pregnancy was uneventful. The
child was born naturally, at term, with low birth weight - 2000g. Postnatal
development was severely delayed (walked at 5 years, first words
at 4 years).
Clinical examination of the child (6 years old) reveals: failure to thrive,
microcephaly (-5,9 SD), narrow mongoloid palpebral fissures, epicanthal
folds, high-pitched voice, micrognathia, displastic ears, severe
mental retardation.
Echocardiography was normal, as well as renal ultrasound. Psychological
examination: IQ 29. A G band karyotyping has been performed
and the result is: 45,XX,der(5)t(5;22)(5p15.1;22q.1)/46XX, der(5)t(
5;22)(5p15.1;22q.1)der (22)(pter→q11.1). FISH analysis confirmed
the translocation and the breakpoint on chromosome 22 (22q11.2;
22q.13). The karyotypes of the parents have been normal.
In conclusion we present a case with delayed diagnosis and complex
karyotype to illustrate the importance of the karyotype and to discuss
genetic counselling in this case.
P03.164
Haploinsufficiency of the gene Quaking (QKI) is associated with
the 6q terminal deletion syndrome
L. Backx1 , J. P. Fryns1 , C. Marcelis2 , K. Devriendt1 , J. Vermeesch1 , H. Van
Esch1 ;
1Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium,
2Department of Human Genetics, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands.
Several subtelomeric aberrations, especially deletions, are associated
with clinically recognizable syndromes, including 1p-, 4p-, 5p-, 9p-, 9q-
, 18p- and 22q-. The recent introduction of array-comparative genome
hybridization in the diagnostic clinic not only enables to identify these
aberrations, but also to delineate the size and locate the position of
the different breakpoints. Comparison of the different sizes and breakpoints
of the affected chromosomal regions permits a first correlation
of the genotype with the phenotype. However, human subtelomere
regions are gene-rich and it still remains difficult to assign the contribution
of each individual gene within the deleted region. Recently, the
Eu-HMTase1 gene was identified as the major gene causing the 9q
subtelomeric phenotype, by studying a balanced translocation involving
chromosomes 9 and X.
Subtelomeric rearrangements involving chromosome 6q have been
reported in a limited number of studies. Although the sizes are very
variable, ranging from cytogenetically visible deletions to small submicroscopic
deletions, a common recognizable phenotype associated
with a 6q deletion could be distilled. The main characteristics besides
mental retardation are hypotonia, seizures, brain anomalies, and
specific dysmorphic features including short neck, broad nose with
bulbous tip, large and low-set ears and a fish-like mouth. We report
a female patient, carrying a reciprocal balanced translocation t(5;6),
presenting with a clinical phenotype highly similar to the common 6qphenotype.
Breakpoint analysis using array painting revealed that the
Quaking (QKI) gene that maps in 6q26 is disrupted, suggesting that
haploinsufficiency of this gene plays a major role in the 6q- clinical
phenotype.