2009 Vienna - European Society of Human Genetics

Cytogenetics
link the separate clinical features to specific chromosomal locations
since the various different regions were just partly overlapping and not
highly specific. However, critical regions for some features have been
delineated, such as heart defects assigned to 8p23.1, encompassing
the GATA4 gene and GNRH1 in 8p21.2 as a candidate gene for hypogonadism.
To further delineate the phenotypic spectrum of interstitial
deletions proximal to 8p23, we studied the clinical and molecular
characteristics of two patients with a 6.75 Mb overlapping interstitial
deletion in the 8p12p21 region and compared these with 17 previously
published cases with an overlapping deletion. The most common characteristics
of interstitial deletions of proximal 8p are developmental delay,
postnatal microcephaly and growth retardation. Other frequently
reported findings are hypogonadism associated with haploinsufficiency
of GNRH1 and ocular problems. Congenital heart anomalies are
also common and might be due to haploinsufficiency of NKX2-6 and/or
NRG1, given that GATA4 is not involved in these proximal deletions.
The aforementioned clinical characteristics should be considered in
the care of patients with a proximal interstitial 8p12p21 deletion.
P03.104
A patient with de novo duplication of 13(q31.1--->qter)
K. Karaer, A. Koç, M. A. Ergün, F. E. Perçin;
Gazi University Faculty of Medicine Department of Medical Genetic, Ankara,
Turkey.
We present a 6 month-old boy, who is the third child of consanguineous
Turkish parents. He was born by spontaneous vaginal birth at 40
weeks, and referred to our clinic due to facial dysmorphic features and
abnormalities.
On his physical examination; weight was 8500 g (qter) in our patient could provide an opportunity to delineate the phenotypic
features due this partial trisomy.
P03.105
Partial trisomy 19p in a girl with general retardation and
dysmorphic signs
C. Duba 1 , B. Günther 1 , G. Webersinke 2 , A. C. Obenauf 3 ;
1 Humangenetische Untersuchungs- und Beratungsstelle, Landes- Frauen- und
Kinderklinik, Linz, Austria, 2 Labor für Molekularbiologie und Tumorzytogenetik,
1. Interne Abteilung, Krankenhaus der Barmherzigen Shwestern, Linz, Austria,
3 Institut für Humangenetik der Medizinischen Universität, Graz, Austria.
Introduction: Array CGH is an essential tool for the detection of microscopically
invisible chromosomal aberrations in retarded and dysmorphic
children. In a female child with general retardation and facial dysmorphisms
a microduplication 19p13.3 was identified. Chromosome
analysis in the parents showed that the mother is carrier of a small
balanced translocation t(14;19)(p11;1;p13.3).
Case report: AF, the second child of healthy parents, was born in May
2005 in the 38 th week of gestation (38+0). She was small for gestational
age (birth weight 1.825g, length 43cm, head circumference 28cm
- all < 3 rd percentile) and showed facial dysmorphisms. At the age of
one year chromosome analysis revealed a normal female karyotype
(400 band stage). AF was presented again at the age of 3 years and
2 months at our genetic counselling unit. Weight was 10,8 kg, height
93cm and head circumference 38cm. She showed a developmental
delay and was able to speak only few words.
Methods and results: Oligonucleotid-based array CGH on Agilent 44K
arrays revealed a 4,68Mb microduplication in 19p13.3 deriving from
a cytogenetically balanced translocation t(14;19)(p11.1;p13.3) in the
mother.
Conclusions: Partial duplication of 19p13.3 is a rare condition with only
few case reports published. We overview the known published cases
and give a comparison with our patient. The influence of the known
genes in the duplicated region will be discussed
P03.106
Identification of a Deletion on Chromosome 3p(12.3) by Whole
Genome Analysis in a Discordant monozygotic twins with a tail
and multiple congenital Anomalies
O. Cogulu, E. Pariltay, A. Alpman, O. Altun, N. Kultursay, R. Ozyurek, F. Ozkinay;
Ege University, Faculty of Medicine, Izmir, Turkey.
Human tail (caudal appendage) is a rare dysmorphic feature and etiologic
mechanisms of human tale are not well understood. Here we
report monozygotic twin brothers who are discordant for the caudal
appendage and multiple congenital anomalies. The index case was
referred to the hospital prematurity and intrauterine growth retardation.
He was born to born to a healthy nonconsanguineous parents at 27
weeks old. On his physical assessment on admission there were micrognathia,
beaked nose, hypospadias and caudal appendage. Caudal
appendage was 2,5-cm-tail-like structurte which was surrounded
by a soft tissue mass at the level of S4. Pathologic examination of the
excised specimen revealed 1.2x1.1x1.0 cm, mature adipose tissue,
connective tissue and hyaline cartilage tissue bone tissue. Echocardiography
revealed juxtaductal aorta coarctation. Karyotype analysis
showed 46,XY. FISH analysis for 22q deletion was negative. Monozygosity
showed by 16 microsatellite markers. We performed genome
wide copy number analysis to monozygotic twins. We hybridized each
other for arrayCGH. By 384k whole genome analysis two neighboring
probes at 3p12.3 has got high Log2 ratios for deletion. High resolution
of chromosome 3 array confirmed ~ 710 Kb deletion where ZNF717,
FRG2C and FAM86D genes are mapped. Although it has been reported
to be a variable region and epigenetic mechanisms are also blamed
in the etiology of human tail, this case is the first report presenting a
CNV in this region with multiple anomalies.
P03.107
characterization of a double ring chromosome 4 mosaicism
associated with bilateral hip dislocation, cortical dysgenesis,
and epilepsy
Y. Soysal 1 , S. Balcı 2 , K. Hekimler 1 , T. Liehr 3 , E. Ewers 3 , J. Schouman 4 , T. Bui 4 ,
N. İmirzalıoğlu 1 ;
1 Afyon Kocatepe University Faculty of Medicine Department of Medical Genetics,
Afyonkarahisar, Turkey, 2 Hacettepe University Faculty of Medicine Department
of Clinical Genetics, Ihsan Doğramacı Children’s Hospital, Ankara, Turkey,
3 Jena University Hospital, Institute of Human Genetics and Anthropology,Kollegi
engasse, Jena, Germany, 4 Department of Molecular Medicine, Clinical Genetics
Unit, Karolinska University Hospital Solna, Stockholm, Sweden.
We present the clinical and cytogenetic findings in a Turkish child with
a de novo mosaic double ring chromosome 4, (46,XY,r(4)[83]/45,XY,-
4[6]/47,XY,r(4),+r(4)[5]/48,XY,r(4),+r(4),+dic r(4)[1]/46,XY[5]) karyotype.
The propositus is a 20-month-old male who was the product of
the first unremarkable pregnancy of nonconsanguineous parents of
19-year-old mother and 28-year-old father. The baby was delivered
vaginally at term and, at birth, weight was 1,700 g (qter::)[67]/46,XY,r(4;4)(::p16.3->qter::
p16.3->qter::)[2]/46,XY[3] by multicolor banding (MCB) technique. The
Wolf-Hirschhorn critical region was preserved. By array CGH the size
of the deletion was delineated as 900 kb in 4p16.3. Additionally, two
small unreported copy number variants were detected on other chromosomes
which do not contain genes associated with developmental
delay. To the best of our knowledge the reported case is unique and
provides further insights in complex rearrangements present espe-