2008 Barcelona - European Society of Human Genetics

Cytogenetics
normalities, cytogenetic study was performed . Balanced translocation
t(1;2)(q25;q21) was detected . His parent’s karyotypes were found to
be normal . In the literature no similar breakpoint region has been reported
.Here we point out the importance of this rare translocation that
may provide a valuable clue to the phenotypic findings and identification
of target loci .
P02.205
Possible post-meiotic origin of the constitutional t(11;22)
T. Kato 1 , H. Inagaki 1 , H. Kogo 1 , T. Ohye 1 , M. Tong 1 , M. Tsutsumi 1 , B. S. Emanuel
2 , H. Kurahashi 1 ;
1 Division of Molecular Genetics, Fujita Health University, Toyoake, Japan, 2 Division
Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA,
United States.
The constitutional t(11;22) is the only known recurrent non-Robertsonian
translocation in humans . The translocation breakpoints occur
within palindromic AT-rich repeats on chromosomes 11q23 and
22q11. In our previous studies, we established translocation-specific
PCR by using the sequence of the translocation junction fragments
from both derivative translocation chromosomes . Using this method,
we successfully detected de novo t(11;22)s in sperm samples from
normal healthy males, but not in lymphoblasts or fibroblasts. To understand
how this translocation occurs during spermatogenesis, we
divided sperm samples into small aliquots prior to DNA extraction and
directly performed translocation-specific PCR. Multiplex PCR allowed
us to detect der(11) and der(22)-specific PCR products of de novo
origin, which were amplified concomitantly from the same aliquots.
This result suggests that the de novo t(11;22) occurs as a reciprocal
translocation . Further, we changed the combinations of primer pairs,
which allowed us to identify dicentric and acentric translocation derivative
chromosomes . Interestingly, these two unusual derivative chromosomes
also appear concomitantly in the same aliquots . Based on the
fact that almost no unbalanced translocation products were identified,
we speculate that de novo t(11;22) translocations are likely to arise at
post-meiotic stages of spermatogenesis .
P02.206
A rare translocation (15;16)(p10;p10) in a normal man
H. Reshadi, C. Azimi, Z. Beheshti, Z. Saltanatpouri;
Department of Genetics, Cancer Institute, Imam Khomeini Medical Center,
School of Medicine, Medical Sciences / University of Tehran, Tehran, Islamic
Republic of Iran.
Whole-arm translocations result from centric fusion of two chromosomes
(usually nonhomologous), followed by a reciprocal exchange
with fusion of entire arms in two derivatives, each with a hybrid centromere
. Nevertheless, there are at least two alternatives: that both
points of interchange will be juxtacentromeric and then each derivative
will conserve its own whole centromere, or that one point will be
centromeric and the other juxtacentromeric, so that one derivative will
have a hybrid centromere and the other will conserve its original but
reduced centromere . Although the underlying mechanisms are still
unknown, detailed molecular analyses have provided evidence that
centromere duplication may predispose to constitutional centric fusion
and consequently favour the occurrence of whole-arm translocations .
Constitutional whole-arm translocations are rather rare and can be
identified in either a balanced or unbalanced state. Most individuals
with balanced forms have a normal phenotype, but may be subfertile .
In contrast, patients with unbalanced whole-arm translocations have
abnormal phenotypes . Here, we describe a 34-year-old healthy married
man who was referred because of consanguinity . His wife and
first child were healthy and they wished to have a second child. Chromosomal
studies were carried on lymphocyte cultures using G-banding
. All mitoses showed a reciprocal whole-arm translocation (15;16) .
The karyotypes of his wife and his child were normal . Other family
members were not available for study. Literature review confirmed that
t(15;16) is very rare .
P02.207
A rare de novo translocation (18;21)(q23;q11.2) in a patient with
Down syndrome
F. Farzanfar, C. Azimi;
Department of Genetics, Cancer Institute, Imam Khomeini Medical Center,
School of Medicine, Medical Sciences / University of Tehran, Tehran, Islamic
Republic of Iran.
We report a 8-year-old boy with clinical features of Down syndrome:
small stature, brachycephaly, flat occiput, small nose, low nasal bridge,
upslanting palpebral fissures, inner epicanthal folds, Brushfield’s spots,
anomalous auricles, dental hypoplasia, short broad hands, Simian
crease, hypoplasia of midphalanx and clinodactyly of fifth fingers, wide
gap between first and second toes, and mental deficiency. Karyotyping
of this patient showed: t (18;21)(q23;q11 .2) . Cytogenetic studies on his
parents and his only sister revealed normal karyotypes . A few reports
have been published concerning familial subtelomeric translocation of
chromosomes 18 and 21, but we could not find any de novo translocation
of 18/21 similar to our case in the literature .
P02.208
A comparison of maternal age among fetuses with trisomy 13
and trisomy 18
I. N. Machado 1 , J. K. R. Heinrich 1 , R. G. Paleari 2 , C. d. Campanhol 3 , K. C. Andrade
4 , R. Barini 4 ;
1 Cell Culture and Cytogenetic Laboratory, Fetal Medicine Unit, CAISM, Unicamp,
Campinas, Brazil, 2 Cell Culture and Cytogenetic Laboratory, CAISM,
Unicamp, Campinas, Brazil, 3 Cell Culture and Cytogenetic Laboratory, CAISM,
Unicamp, Campinas, Brazil, 4 Fetal Medicine Unit, CAISM, Unicamp, Campinas,
Brazil.
Objective: To evaluate the difference of maternal age among fetuses
with trisomy 13 and trisomy 18 .
Methods: A retrospective review of the cytogenetic laboratory databases
identified all cases of prenatally diagnosed trisomy 13 and trisomy
18 from January 1997 to December 2007, and maternal age was recorded
. Ages were compared by unpaired t test, with a power of 44 .6%
because the two groups had no normal distribution . A “p” value < 0 .05
was considered statistically significant.
Results: 61 affected fetuses were included: 38 cases of trisomy 18 and
23 cases of trisomy 13 . The mean maternal age in cases of trisomy 13
was 30 .3 years (16-44 years, sd = 7 .8 years), and in cases of trisomy
18 was 29 .9 years (16-46 years, sd = 9 years) . The difference in mean
maternal age between these two groups shown a “p” value = 0 .82 . The
frequency of patients younger than 35 years of age for trisomy 18 was
65 .7% (n=25) and for trisomy 13 was 65 .2% (n=15) .
Conclusion: Our study showed that the difference in mean maternal
age among fetuses affected by trisomy 13 and trisomy 18 was not
significant. It was shown a trend of more cases diagnosed in patients
younger than 35 years old . However, more data are needed to establish
whether this is a true phenomenon or a bias of the population
studied .
P02.209
A case of de novo trisomy 12p
T. G. Tsvetkova, N. V. Shilova, V. A. Galkina, N. V. Kosjakova, I. A. Mandron,
T. V. Zolotukhina;
Research Centre for Medical Genetics of RAMS, Moscow, Russian Federation.
We are reporting the clinical and cytogenetic studies on a 6 months-old
boy who was referred for karyotyping because of distinct craniofacial
dysmorphic features. Phenotype of proband included: acrocephaly, flat
occiput, mid-face hypoplasia, upslanting palpebral fissures,hypoplastic
supra-orbital ridges and high narrow palate,dysplastic ears, brachydactyly,
broad thorax and pectus excavatum . Psychomotor and mental
retardation was marked . Conventional cytogenetic analysis of patient
using GTG- banding revealed 47,XY,+mar karyotype . Supernumerary
marker chromosome ( SMC ) resembled 21q or 12p and had AgNOR
on short arm . The karyotypes of parents were normal . FISH analysis
with LSI 21(21q22 .13-q22 .2) and WCP 12 DNA -probes (Vysis,Abbott)
and DAPI contrstaining was performed . SMC was LSI 21-, WCP12+ .
FISH analysis showed that SMC was composed of chromosome 12p
and short arm of one of acrocentric chromosomes . Inverted DAPI-
staining revealed that short arm of the SMC contained only heterochromatic
DNA and NOR of acrocentric chromosome . Therefore we
proposed that this part of SMC has not a pathological phenotype effect
. An adverse effect on the phenotype is caused of a de novo trisomy
12p . Probably this chromosome is a result of parental meiotic
mutation. Use of FISH with high-specific DNA-probes increases the
quality of cytogenetic diagnosis and allowes one to base further recommendation
for genetic counseling