2008 Barcelona - European Society of Human Genetics

Cytogenetics
netic study allows the correct diagnosis of such cases and provides an
early genetic counselling in patients with high recurrence risk .
P02.156
inversions detected in a study of 79920 prenatal and postnatal
karyotypes
C. Hernando, R. Pujol, L. Cusidó, D. Carbonell, M. Rigola, R. Fernández, S.
Escorihuela, N. Pujol, J. Barderi, C. Muñoz, L. Maynes, C. Preciado, J. Martos,
S. Leal, O. Casablancas, E. Rodríguez, B. García, M. Cuartero, M. Pleguezuelos,
J. Hernández, P. Grao;
CERBA Internacional, Sabadell, Spain.
Inversions are intrachromosomal rearrangements apparently balanced,
generally without consequences for the carrier; however, an
abnormal phenotype may be expressed if a breakpoint disrupts a critical
gene . The observed phenotype depends on the length of the inverted
segment, number of chiasmas produced and the genes of the
involved region .
The incidence of pericentric and paracentric inversions in general population
ranges from 0,12 to 0,7/1000 and 0,1 to 0,5/1000 in newborns
respectively . The frequency in the general population is estimated at
1-2% . It is 13 times higher among infertile men than in general population
. Indeed, these chromosomal abnormalities can perturb spermatogenesis
and lead to the production of unbalanced gametes .
Out of 79920 cases that came in for genetic counseling during the
last 6 years, we have detected 146 chromosome inversions, excluding
polymorphic inversions of chromosome 9 . Among these cases, 63
have been prenatally detected and 83 postnatally, 108 are pericentric
inversions and 33 cases are inherited .
We have identified inversions for chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 14, 18, 20, X and Y .
Abnormal phenotype has been observed in 5 postnatal cases (3,4%) .
In 8 cases, the reason for referral was infertility or miscarriages, nonetheless
ascertainment was primarily incidental .
In conclusion, our study has revealed an incidence of inversions in
agreement with what it was expected . According to the literature, we
have found that the presence of an inversion is rarely linked with an
abnormal phenotype or abnormal progeny, nevertheless caution is
recommended when counseling .
P02.157
De novo isodicentric X chromosome: report of two new cases
M. Pilechian Langeroudi, C. Azimi, M. Khaleghian, F. Farzanfar;
Department of Genetics, Cancer Institute, Imam Khomeini Medical Center,
School of Medicine, Medical Sciences / University of Tehran, Tehran, Islamic
Republic of Iran.
Isodicentric X chromosomes with an Xq deletion are uncommon . Phenotypes
are variable and correlate with the existence of mosaic or nonmosaic
isodicentric X chromosomes and also depend on the amount
of deleted genetic material in the patients .
We report two new cases which were referred to our Department due
to primary amenorrhea . First case was 20-year-old, 158 cm height,
54 kg weight and with intermediate IQ . She presented with the typical
features of Turner syndrome: broad and shield-shaped thorax,
small breasts, wide-spaced nipples, cubitus valgus, short and thickened
neck, low hairline, scant axillary and pubic hair, infantile external
genitalia . Sonography report showed lack of ovaries and hypoplasia of
uterus . Her thyroid hormones were normal but her FSH and LH were
high . Karyotyping was performed on peripheral blood lymphocytes using
different banding techniques according to standard methods . Her
karyotype was: 46, X, idic (X)(q24) . Chromosome studies of her parents
and her three sibs revealed normal .
Second case was 18-year-old, 155 cm height, 62 kg weight and subnormal
intelligence . Her clinical features were: shield-like chest, no
breast development, widely spaced nipples, pigmented nevi, normal
neck, absence of axillary hair, limited pubic hair, infantile external genitalia
. Her sonography revealed horseshoe kidney, hypoplastic uterus
and absence of gonads . She had elevated FSH and LH . Her karyotype
was: 45, X [80%] / 46, X, idic (X)(q22) [20%] . Cytogenetic investigations
of her parents and her four sibs revealed normal .
P02.158
Jumping translocation in a phenotypically normal male - a study
of mosaicism in spermatozoa, lymphocytes and fibroblasts
E. Iwarsson, S. Sahlén, A. Nordgren;
Dept of Molecular Medicine, Stockholm, Sweden.
Jumping translocation refers to a rare type of mosaicism, in which
the same chromosome segment is translocated to different chromosome
sites in different cell lines . We report a case of mosaicism for two
cell lines, each cell line containing a different de novo Robertsonian
translocation with the common breakpoint in the centromeric region on
chromosome 13, in a phenotypically normal male . The karotype was
defined as: 45,XY,der(13;13)(q10;q10)/45,XY,der(13;15)(q10;q10)de
novo. The relative occurrence of the two clones in lymphocytes, fibroblasts
and spermatozoa was determined using karyotype analysis
and fluorescence in situ hybridisation (FISH). Karyotype analysis of
lymphocytes revealed 57 % der(13;13) cells and 43 % der(13;15) cells
and for skin fibroblasts the figures were almost identical (56 % and
44 % respectively) . FISH analysis showed 55 % balanced nuclei for
unselected spermatozoa and after swim-up selection the number of
balanced spermatozoa decreased to 41 % . In addition, 16 % of the unselected
spermatozoa and 27 % of the spermatozoa after swim-up selection
carried an additional chromosome 13, indicating a high risk for
trisomy 13 offspring (Table 1) . To the best of our knowledge this is the
first study on meiotic chromosome segregation in spermatozoa from
a jumping translocation carrier as well as a Robertsonian der(13;13)
carrier. The reproductive significance of the abnormality and its implications
will be discussed .
table 1 Results from FISH-analysis of one thousand spermatozoa
Chromosome 13/15 13/15* 13/15* 13/15 13/15 13/15 13/15 13/15
No of signals from chromo-
1/1 0/1 2/1 1/0 1/2 2/2 2/0 3/1
some 13/15
Before swim-
54,80 26,10 15,70 1,80 0,80 0,20 0,30 0,30
% of sperup selection
matozoa After swim-up
40,60 30,50 26,60 1,50 - - 0,30 0,50
selection
Segregation mode Alternate Adjacent 3:0† Other††
*These columns also contain segregation products of the homologous Robertsonian
translocation der(13;13), which are not true adjacent segregation. †Using this twocolour
FISH approach, it is not possible to differentiate between diploid spermatozoa
and 3:0 segregation as both show two hybridisation signals for the probes used. †Nuclei
with an unexpected combination of signals according to the possible segregation
modes are classified as other.
P02.159
Low level mosaicism homologous Robertsonian translocation
(21;21) in a mother of boy with unbalanced der(21;21)
S. Teofilova 1,2 , M. Bulatović 1,2 , O. Miljanović 1,2 ;
1 Center for Medical Genetics and Immunology-Clinical Center of Montenegro,
Podgorica, Montenegro, 2 Institute for Children s Disease- Clinical Center of
Montenegro, Podgorica, Montenegro.
Parents of fetuses and children with unbalanced homologous acrocentric
rearrangements are rarely found to be carriers or mosaic for the
same rearrangements . Carriers of homologous acrocentric rearrangements
(Robertsonian translocation) phenotypically normal they are at
very high risk of having multiple spontaneous abortions and chromosomally
abnormal offspring . Very frequently fetuses with homologous
Robertsonian translocation arise postzygotic and are of maternal and
parental origine .
We report about a fenotypycal healthy woman with low level mosaicism
for Robertsonian translocation (21;21). She delivered her first child in
21 year and he had Down′s syndrome. Chromosomal preparations
were made and banded using standard tehniques . The karyotype of
the boy was 46,XY,t(21;21),+21 . After genetic counseling were made
analysis parents. Father had normal karyotype 46,XY. Mother′s chromosomes
analysis showed very low lavel mosaicism, karyotype 46,XX
[95]/45,XX,t(21;21) [5],wich was detected becouse analysis made in a
large number of cells .
After prenatal chromosomal diagnostic this woman delivered two
healthy boys . Fourth pregnancy was aborted becouse prenatal cytogenetic
analysis fetus showed unbalanced Robertsonian translocation .
Identification of mosaicism allowes for accurate genetic counseling
and disussion of reproductive options .