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

Cytogenetics
P0389. An age based cytogenetic analysis in prostate cancer
patients in Southern India
B. Vellingiri, B. Lakshman Kumar, K. Sasikala;
Prostate cancer is a malignant tumor that arises in the prostate gland.
It is located near the bladder and rectum, which creates and stores
components of semen.Prostate cancer is the second most leading
cause of death in men due to any cancer type in India. Human prostate
cancer is characterized by multiple gross chromosome alterations.
However the specific genes involved in the development of prostate
tumors are still largely unknown. The chromosomal region largely affected
in prostate cancer patients are 1, 6, 7, 8, 10, 13, 16, 17, 18, X
and Y.
Since chromosomal abnormalities are involved in tumorigenesis, we
selected karyotypic analysis in Prostate cancer patients in Southern
India patients.. Prostate size in the patients is increased proportional
to their age, so we performed an age based cytogenetic analysis. In
the present study blood samples were collected from various hospitals
in and around Tamilnadu.
Out of the 40 blood samples (Prostate cancer samples) 36% of the
slides showed chromosomal aberrations such as deletions, translocations,
mosaics and inversion. Among three groups Group II and Group
III showed majority of chromosomal abnormalities when compared to
Group I. In Group II ,46 XY,del (1q-),46, XY inv (16), 46,XY,t(6q;16q+),
46 XY,del(5p-), 46,XY,inv(9), 46XY,del(8q-) chromosomal aberrations
were observed. In Group III ,46,XY,t(6q;16q+), 46,XY,/46,XY del (5p-
), 46 XY,del (Yq-), 46 XY, del (1q-) are identified. The chromosomes
mainly affected in the present study include 1, 6, 5, 8 and 16. Identification
of chromosome alterations may be helpful on arising better
therapeutic strategies in future.
P0390. Report of a patient with duplication of proximal 20q:
clinical and cytogenetic characterization
N. Marle1 , L. Faivre2 , P. Callier1 , C. Thauvin2 , A. Mosca1 , F. Mugneret1 ;
1 2 Laboratoire de Cytogénétique, CHU Le Bocage, Dijon, France, Centre de
Génétique, Hôpital d’Enfants, Dijon, France.
Partial trisomies of the long arm of chromosome 20 are rare. Most
cases reported in the literature are the result of malsegregation of a
parental translocation and are complicated by additional partial monosomy
or trisomy of another chromosome region. Here we report the
first child of healthy non consanguineous parents with pure 20q11.2
trisomy. He was first referred at age 2 months for facial dysmorphism
(prominent metopic suture, epicanthic folds, peripalpebral oedema,
small and thick ears, prominent cheeks) and standard karyotype appeared
normal. He walked independently at age 25 months and speech
delay was noted. At 3 years of age, measurements were within normal
limits. Cytogenetic analysis of cultured peripheral blood lymphocytes
with high resolution banding revealed a male karyotype with an apparent
interstitial duplication in the long arm of chromosome 20 of band
20q11.2. FISH studies with a whole chromosome paint probe (WCP)
specific for chromosome 20 confirmed that the additional material was
originated from chromosome 20. FISH studies with M-BAND and BAC
probes specific for the long arm of chromosome 20 confirmed that the
duplicated band was restricted to band 20q11.2. The full karyotype
was therefore 46,XY,dup(20)(q11.1q12).ish dup(20)(WCP20+,RP5-
1184F4++,RP11-382A12++). Both parents had a normal karyotype, in
favour of a de novo duplication. To the best of our knowledge, only
four cases of pure 20q trisomy resulting from duplication have been
reported. We compare clinical features and cytogenetic findings of our
case with the previously reported observations.
P0391. Array CGH delineation of de novo pure partial trisomy
17q24.3-qter due to a terminal duplication in one-year-old girl
M. Stefanova1 , K. Kovacheva2 , M. Simeonova2 , H. Rose3 , M. Kirchhoff3 ;
1 2 Medical University, Plovdiv, Bulgaria, Medical University, Pleven, Bulgaria,
3Rigshospitalet, University of Copenhagen, Denmark.
Pure partial trisomy 17q24.3-qter is only described in a few cases,
but it is an increasingly recognized clinical entity (Bridge et al., 1985;
Orye and van Bever, 1985; Schwanitz et al., 1988; Ohado et al., 1989;
Ghaffari et al., 1998). The characteristic features of this chromosome
aberration include varying degrees of mental retardation, short stature,
narrow forehead, macrostomia, a simple and long philtrum, low
posterior hairline, and genital anomalies (Schinzel, 2001). Here we
report a detailed clinical and molecular investigation of a one-year-old
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girl with a de novo dup(17)(q24.3-qter). She presented with severe
developmental and growth delay, microcephaly, hypotonia and the following
dysmorphic features: narrow forehead, upslanting palpebral fissures,
hypertelorism, low-set posteriorly rotated ears with pronounced
antihelix, large mouth, a simple and long philtrum, micrognatia, low
posterior hairline, thenar hypoplasia, cutis marmorata, hypoplastic labia
and prominent clitoris. No brain or inner organ anomalies were
found. Conventional cytogenetics revealed an additional material on
17qter identified by 244k Agilent oligoarrays CGH analysis as a duplication
of chromosome region 17q24.3-qter with a breakpoint between
66,580,674 and 66,678,854bp. Our case is the first pure duplication
of chromosome region 17(q24.3-qter) confined by array CGH studies
and it shows the usefulness of recently developed array CGH technology
to accurately characterize chromosome abnormalities, especially
when they are de novo.
P0392. A novel reciprocal translocation t(l ;17) detected in a
woman with recurrent abortion
F. Manoochehri, S. Tootian, M. Rahnama, F. Razazian., F. Mortezapour barfi,
M. Zamanian, F. Nasiri, S. Soleymani., F. Mahjoubi;
Iran blood Transfusion Organization, 2 National Research Institute for Genetic
Engineering and Biotechnology, Tehran, Islamic Republic of Iran.
In the present study, we present a novel reciprocal translocation t(l;17)
(17pter.17p36.2::1p13 1pter)(1pter.1p13::17p36.2 17qter). A couple
was referred to us for chromosomal analysis because of the history of
two spontaneous abortions. Both husband and wife had a phynotypically
normal child from their previous marriage. There had been no history
of repeated spontaneous abortions in their families. Chromosomal
study was performed on peripheral blood lymphocytes. A balanced reciprocal
translocation between chromosomes 1 and 17 was observed
in the wife. Therefore, the karytotype was assecced as 46,XX,t(l;17)
(17pter.17p36.2::1p13 1pter)(1pter.1p13::17p36.2 17qter). The husband
had normal karyotype. To the best of our knowledge these breakpoints
have not been reported previously. Thus, we can assume that
this is the first report of a translocation between chromosome 1 and 17,
with such breakpoints
P0393. Importance of the correct designation of breakpoints for
structural chromosomal aberrations in preimplantation genetic
diagnosis strategies
S. A. Tashkandi1 , A. Mantzouratou1 , A. Mania1 , E. Fragoul1 , A. Doshi2 , S. Nuttall2
, K. Fordham1 , P. Serhal2 , J. D. A. Delhanty1 , J. C. Harper1 ;
1 2 University College London, London, United Kingdom, University College London
Hospital, London, United Kingdom.
Introduction: Three couples were referred to our PGD centre where the
male partner was a carrier of a balanced reciprocal translocation. PGD
protocols were designed according to the provided karyotypes. During
the workup it was found that the breakpoints reported in the karyotypes
were incorrect.
Methods:
Case 1: 46,XY,t(14;16)(q13;q11.1) and oligospermia
Case 2: 46,XY,t(1;4)(q12;q33) and poor sperm parameters
Case 3: 46,XY,t(1;21)(q21.3;q22.1) and primary infertility
FISH protocols were designed using probes for the chromosomes involved
in each translocation. Protocols were optimised on metaphase
spreads from both partners.
Results: Using the individual FISH protocols determined from the
karyotype, it was found that in all three cases the incorrect break points
had been reporeted.
Case 1: Breakpoint on 16q11.1 was incorrect as the breakpoint was
below this region. The derivative chromosome 14 would be missed in
the balanced embryo.
Case 2: Breakpoint on 1q12 was incorrect as the breakpoint was at the
centromere. This could have led to an extra signal for the centromere
of chromosome 1 in a balanced embryo.
Case 3: Breakpoint on 1q21.3 was incorrect as the correct breakpoint
was 1q12. This could have led to an extra signal for the centromere of
chromosome 1 in a balanced embryo.
New protocols were designed and the patients underwent PGD.
Conclusions: This study highlights the need to test PGD FISH protocols
on metaphase spreads from the patient to confirm the karyotype.
Incorrect designation of breakpoints could lead to the use of an uninformative
protocol which could result in a misdiagnosis