European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cytogenetics
ing of complex examination of ejaculate from patients with infertility.
Supported by CRDF&RFBR.
Kurilo et al. Probl. Repr.(rus) 1995.v.3.p.33
P0409. Unusual small supernumerary marker chromosome
(sSMC) in a woman with Triple X syndrome
S. Soleimani 1 , F. Razazian 2 , F. Nasiri. 1 , S. Tootian. 1 , M. Zamanian. 1 , M. Rahnama
1 , F. Mortezapoor 1 , F. Mahjobi 3 ;
1 1) The Blood Transfusion Organization research center, Tehran, Iran, tehran,
Islamic Republic of Iran, 2 The Blood Transfusion Organization research center,
Tehran, Iran, tehran, Islamic Republic of Iran, 3 NRCGEB &The Blood Transfusion
Organization research center, Tehran, Iran, tehran, Islamic Republic of
Iran.
Small supernumerary marker chromosomes (sSMC) are small additional
chromosomes. sSMC have been reported previously in four
types of syndromes associated with chromosomal imbalances: in approximately
150 cases with Turner syndrome, 26 cases with Down
syndrome and only one case each with Klinefelter syndrome and
“Triple-X”-syndrome. Here we report the second case with an sSMC
detected in addition to a Triple X karyotype.
The reported patient was referred to our clinic because of mild mental
retardation, developmental delay, dysmorphic face. Three cell lines
was detected, one with 47, XXX, one with 46, X, +mar, and one with
46, XX. The presence of a marker chromosome in this case generally
implicates a sex chromosome origin. It may also originate from a nonsex
chromosome.
P0410. Sex chromosome aberrations associated with
reproductive failure problems
M. D. Miskovic1 , M. Guc-Scekic1,2 , S. Cirkovic1 , N. Lakic1 , A. D. Krstic1 , D.
Radivojevic1 , T. Lalic1 , M. Djurisic1 ;
1Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade,
Serbia, 2Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Patients with sterility, primary amenorrhea, azoospermia or other reproductive
failure have indication for cytogenetic analysis. The aim of
this study was to evaluate the contribution of sex chromosomal abnormalities
in such cases. We report here results of 22 patients, who visited
Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”
from 1996-2006.
Cytogenetic analysis was performed on 72-hour peripheral blood
culture lymphocytes. Metaphases were karyotyped using G and C
banding technique for chromosome identification. Molecular-genetic
methods are used for solving cytogenetic dilemmas - FISH with X centromeric
region specific probes (DXZ1) and PCR with primers for SRY
gene and heterochromatin region of Y chromosome (HRY).
In 3 males with azoospermia karyotype: 47,XXY was found. At 6 cases of
male sterility following sex chromosome aberrations were seen: 47,XXY;
46,i(X)(q10)Y; 46,XY[33]/47,XYY[4]; 46,XY[28]/47,XYY[8]; 46,X,der
(Y)t(Y;Y)(p11.3;q11.1) and 46,X,r(Y)(p11.3;q12),inv(9)(p12q13)[22]/
45,X,inv(9)(p12q13)[3]. In last two cases we provided presence of
SRY gene and HRY using PCR method.
Following karyotypes: 46,X,i(X)(q10); 46,X,i(X)(q10)[30]/45,X[3];
47,XXX[3]/48,XXXX[1]/46,XX[96] were associated with female sterility.
Primary amenorrhea diagnosed in 11 female was combined with
karyotypes:
45,X; 46,X,del(X)(q13); 45,X[34]/46,Xder(X?)[30] and 46,XY(8 cases).
To determine numerical aberration of X chromosome and define mosaic
karyotype FISH with X - centromeric region probe was used. The
presence of Y chromosome was confirmed with PCR.
Cytogenetic and molecular genetic approach is very important step to
establish the genetic etiology in reproductive failure abnormalities. Our
study shows that sex chromosomes aberrations are often associated
with these disorders, which is crucial for genetic counseling and future
possible preimplantation management.
P0411. Application of FISH to identification of subtelomeric
rearrangement in cases of intellectual disability and in a couples
with reproduction problem
J. Bogdanowicz, A. Ilnicka, B. Pawlowska, A. Tomankiewicz-Zawadzka, B.
Sobiczewska, E. Zdzienicka, J. Kubalska, S. Gawlik-Zawiślak, A. Górna, J.
Zaremba;
12
Institute of Psychiatry and Neurology, Warsaw, Poland.
FISH technique with subtelomeric probes was applied for cytogenetic
examination of 96 patients with normal karyotype obtained with routine
banding methods. Patients were divided into two groups. Group I composed
of 76 patients with intellectual disability, dysmorphic features;
group II composed of 10 couples (20 individuals with history of several
miscarriages and offspring with abnormal phenotype. In group I in 4
(5%) cases subtelomeric aberrations were found: 3 cases of subtelomeric
deletion 1p36 ( 2 de novo and one due to inherited 1;12 translocation
(with resulting monosomy of subtelomeric region1p and trisomy
of subtelomeric region of 12q). In all 3 cases phenotypic features were
characteristic of 1p deletion syndrome.
In the case No 4 balanced de novo translocation 19;22 was found.
In the other 3 cases of group I subtelomeric polymorphic variants of
chromosome 2q (inherited deletion) and 7q (inherited duplication)
were found.
In group II three families with subtelomeric translocations were diagnosed:
(7;14), (4;7) and (9;18): in two families chromosome 7q
subtelomeric deletion was diagnosed ( one of them prenatally); holoprosencephaly
and associated abnormalities (cleft lip and palate,
microcephaly) were observed in these cases (most probably sonic
hedgehog gene being involved).
P0412. Molecular characterization of a mosaicism with a
complex chromosome rearrangement: Evidence for coincident
chromosome healing by telomere capture and neo-telomere
formation
E. Chabchoub 1 , L. Rodríguez 2 , E. Galán 3 , E. Mansilla 2 , M. L. Martínez-Fernandez
2 , M. L. Martínez-Frías 2 , J. P. Fryns 1 , J. R. Vermeesch 1 ;
1 Centre for Human Genetics - University Hospital Gasthuisberg, Leuven, Belgium,
2 Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC)
del Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de
Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain, 3 Servicio de
Pediatría. Hospital Materno Infantil de la seguridad Social de Badajoz, Badajoz,
Spain.
Broken chromosomes, such as terminal deletions, must acquire new
telomeric “caps” to be structurally stable. Chromosome rescue could
be mediated either by telomerase through neo-telomere synthesis or
by telomere capture. The first process is the main mechanism healing
broken chromosomes in germline cells, the latter in somatic cells. Here,
we describe a clinical and molecular study of a 14 year-old girl presenting
with mental retardation, facial dysmorphism, urogenital malformations
and limbs anomalies. High resolution G banding shows a de novo
complex chromosome rearrangement in mosaic with two different cell
lines, one cell line with a deletion 9pter and one cell line carrying an
inverted duplication 9p and a non-reciprocal translocation 5pter fragment.
Using array comparative genomic hybridization (a CGH), fluorescence
in-situ hybridization (FISH) and polymorphic markers we deduced
the most likely sequence of events that generated this complex
mosaic. Surprisingly, we show evidence for simultaneous stabilization
of rearranged chromosomes by telomere capture and neo-telomere
synthesis. During embryogenesis, a double-strand break occurred
on the paternal chromosome 9. Following mitotic separation of both
broken sister chromatids, one acquired a telomere via neo-telomere
formation, while the other generated a dicentric chromosome which
underwent breakage during anaphase, giving rise to the del inv dup(9)
that was subsequently healed by chromosome 5 telomere capture.
P0413. Breakpoints analysis of a balanced de novo translocation
t(3;18)(q13.13;q12.1) in a patient with Opitz C trigonocephaly
syndrome
T. Kaname 1,2 , K. Yanagi 1 , Y. Chinen 3 , K. Yoshiura 4,2 , N. Niikawa 4,2 , K. Naritomi 1,2 ;
1 Department of Medical Genetics, University of the Ryukyus, Nishihara-cho, Japan,
2 SORST, JST, Kawaguchi, Japan, 3 Department of Pediatrics, University of
the Ryukyus, Nishihara-cho, Japan, 4 Department of Human Genetics, Nagasaki
University Graduate School of Biomedical Sciences, Nagasaki, Japan.
We present molecular characterization for a balanced translocation
t(3;18)(q13.13;q12.1) in a male patient. He had clinical manifestations
of the Opitz C trigonocephaly syndrome (OCTS) including trigonocephaly,
a prominent metopic ridge, upslanting palpebral fissure, epicanthal
folds, high-arched palate, thick and irregular alveolar ridge,
long philtrum, redundant nuchal skin, a genesis of the corpus callosum,
and hypotonia, who had been recently reported [Am. J. Med. Genet.