2008 Barcelona - European Society of Human Genetics

Cytogenetics
ing the Illumina Infinium 317 K SNP array system, and subsequently
confirmed by fluorescence in situ hybridisation (FISH) analysis. The
deletion appeared to have arisen de novo . The IGF1R (insulin-like
growth factor 1 receptor) and the NR2F2 genes were situated within,
but the OCA2 (oculocutaneous albinism II) gene (formerly called the P
gene) was located outside the deleted region. Clinical findings in our
patient were compared with previously reported cases carrying terminal
deletions of 15q26 .2 . This allowed us to expand the clinical phenotype
of terminal 15q26 .2 deletions and to indicate candidate genes for
several phenotypic features .
P02.173
Array cGH with genomic DNA extracted from peripheral
blood detects overrepresentation of 12p material in a boy with
Pallister-Killian syndrome features
S. Uhrig 1 , A. Obenauf 1 , U. Gruber-Sedlmayr 2 , S. Langer 3 , M. R. Speicher 1 ;
1 Institut für Humangenetik, Graz, Austria, 2 Abteilung für Allgemeine Pädiatrie,
Universitätsklinik für Kinder- und Jugendheilkunde, Graz, Austria, 3 Institut für
Humangenetik, Technische Universität München, München, Germany.
Pallister-Killian syndrome (PKS) is a rare disorder characterized by
multiple congenital anomalies . The cytogenetic hallmark change in
PKS is the presence of a supernumerary isochromosome 12p (i(12p)),
which is usually limited to skin fibroblasts. Here we report on a 11-yearold
boy with clinical features suggestive for PKS . Amniocentesis performed
elsewhere did not show any abnormality . At the age of 9 years
he developed seizures requiring anticonvulsant treatment . When we
saw the boy at age 11, he had a coarse face with hypertelorism, a
broad nasal bridge, a highly arched palate, long philtrum and prominent
lower lip . On the right forehead and chest were streaks of hypo-
and hyperpigmentation . G-banding analysis of peripheral lymphocytes
revealed a mosaic karyotype with a small metacentric supernumerary
marker chromosome (SMC) in about 30% of metaphases . Array CGH
using genomic DNA extracted from peripheral blood identified overrepresentation
of 12p, however, several 12p-clones showed a balanced
ratio profile, which was not compatible with an isochromosome 12p.
Therefore, we further characterized the marker by forward painting with
subtelomeric BAC-clones for 12p (GS-496A11) and 12q (12q-21K18) .
While both clones showed regular signals on both chromosomes 12,
the marker had a signal on only on one end . Hybridising the centromere
specific probe for chromosome 12 both normal chromosomes
12 and the marker showed unique hybridization signals . At present,
we are using additional clones to characterize this der(12) further . Our
results suggest that array CGH is suitable for the detection of low level
mosaics and may thus complement conventional banding analyses .
P02.174
molecular cytogenetic study of the partial monosomy 21q
L. Nazaryan1 , S. Midyan1 , R. S. Møller2,3 , R. Ullmann4 , N. Tommerup2 ;
1 2 Center of Medical Genetics and Primary Health Care, Yerevan, Armenia, Wilhelm
Johannsen Centre for Functional Genome Research, Institute of Cellular
and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark,
3 4 Danish Epilepsy Centre, Dianalund, Denmark, Max Planck Institute for Molecular
Genetics, Berlin, Germany.
INTRODUCTION: Partial monosomy 21 is rare and only a few cases
have been reported so far . Furthermore, the extent of the deletions has
not been determined in the majority of these cases, which makes phenotype-genotype
correlation difficult. In this study we present a 1 year
old girl with severe neonatal hypotrophy, microcephaly, mental retardation,
large low-set and deformed ears, wide forehead, strabismus,
massive nose, long philtrum, wide mouth with thin lips, micrognatia,
pectus excavatum, spinal curvature and clubfoot .
METHODS: The patient was analysed using conventional cytogenetics,
array CGH and FISH . Array CGH was carried out using a submegabase
whole genome tiling path BAC array and the results were
verified by FISH analysis.
RESULTS: Cytogenetic analysis of the patient and her parents revealed
a de novo deletion of chromosome 21q22 .11-qter . The deletion
was further characterized by array-CGH which justified the borders
of the deletion to 21q22 .12-qter (chr21:35,860,000-46,940,000, hg17) .
In addition we detected a 0,9 Mb duplication on chromosome 17q12 .
Array CGH was also performed on the cytogenetically normal parents
and the results showed that the duplication was inherited from the phenotypically
normal father .
CONCLUSION: In the present study we analysed a patient with a
terminal deletion of 21q22 . The clinical manifestations of our patient
are mostly consistent with previously reported cases . However, since
the extent of the majority of these deletions has not been determined,
though phenotype-genotype correlation is difficult. We therefore recommend
that patients with chromosomal abnormalities diagnosed by
conventional karyotyping should be reinvestigated by array CGH .
P02.175
Partial trisomy of chromosome 10q due to the paternal balanced
t(10;22)(q24;p11)
T. Cora1 , H. Acar1 , M. Acar1 , B. Alımcı1 , R. Örs2 ;
1Dept. of Medical Genetics, Medical Faculty, Selcuk Univ, KONYA, Turkey,
2Dept. of Pediatri, Medical Faculty, Selcuk Univ, KONYA, Turkey.
The distal part of the long arm of chromosome 10 trisomy is a well
defined, but rare syndrome. This chromosomal abnormality is almost
the result of an balanced translocation from the parents . In the present
report, we present a family having a girl with balanced translocation,
a healthy girl and a malformed female infant with the pure partial trisomy
of the long arm of chromosome 10q (q24 leads to qter), resulting
from an unbalanced segregation of a paternal balanced translocation
t(10;22)(q24;p11) . In this patient, physical examination showed to have
abnormal phenoty such as microcephaly, small nose, depressed nasal
bridge, blepharophimosis, micrognathia, hypotonicity and growth retardation.
These clinical findins are compared with the other previously
described cases with the trisomy 10q in the literature .
P02.176
Report of a dysmorphic case from IRAN with a new finding, and
structural abnormality in the long arm of chromosome 1.
F. Hadipour 1 , Z. Hadipour 2 , F. Behjati 3,4 , Y. Shafeghati 3,1 ;
1 Sarem Women’s Hospital, Tehran, Islamic Republic of Iran, 2 Sarem Women’s
hospital, Tehran, Islamic Republic of Iran, 3 Genetics Research Center, Tehran,
Islamic Republic of Iran, 4 Sarem Women’s Hospital,, Tehran, Islamic Republic
of Iran.
Background: Partial trisomy of 1q42 is one of the structural Chromosome
abnormalities with a distinctive phenotype .
Material and Method: Here in we report a 1-year-old Iranian girl referred
to our genetics center because of neuro-developmental delay
and dysmorphic findings.
Cardinal features were: trigonocephaly, microcephaly, spastisity, sunken
eyes, prominent forehead, low set and malformed ears (with posterior
rotation and abnormal helix), micrognathia, long philtrum, carplike
mouth, frontal bossing, high palate, high nasal bridge, high arched eyebrows,
short neck, strabismus, and asymmetric face and locked jaw,
abnormal and small hands and feet, brachydactily of fingers and toes,
flat feet, congenital hearth disease, dysplastic nails, simian crease in
right hand and abnormal sole in the left hand .
Chromosme study: according to the MR, and MCA we carried out chromosome
analysis by high resolution GTG banding technique . The result
was a structural abnormality, a duplication in1q42 region . Parents
were investigated and they were normal .
Conclusion: our study showed that this chromosome Abnormality was
de novo in this case . So, we should consider structural and numerical
chromosome abnormalities in the patients, with MCA+MR . Microcephaly
is a new finding for this locus, and was not reported before.
Keywords: Partial trisomy of 1q42, trigonocephaly, microcephaly,
P02.177
X chromosome centromere instability: an epiphenomenon of
ageing or of Alzheimer disease?
L. Zivkovic 1 , B. Spremo-Potparevic 1 , Z. Milicevic 2 , N. Djelic 3 , V. Bajic 4 ;
1 Faculty of Pharmacy, Institute of Physiology, Department of Biology and
Human genetics, Belgrade, Serbia, 2 “VINCA” Institute of Nuclear Sciences,
Laboratory for Molecular Biology and Endocrinology, Belgrade, Serbia, 3 Faculty
of Veterinary Medicine, Department of Biology, Belgrade, Serbia, 4 Institute of
Biomedical Research Galenika, Belgrade, Serbia.
Premature centromere division (PCD) as a cause of improper chromosome
separation is found in ageing cells, Alzheimer disease patients,
various chromosome instability syndroms and cancers . Gender plays
an important role in the pathogenesis of AD and can influence the risk
of developing AD . Is PCD a citogenetic marker of this disease, or only
epifenomen of ageing? PCD phenomenon of metaphase chromosome