2008 Barcelona - European Society of Human Genetics

Cytogenetics
sented with ambiguous genitalia . The 1 st case was reared as male and
had right palpable gonad, uterus and left streak gonad . Its karyotype
was 45,X/45,der(X)/46,X,der(X) .ish der(X)t(X;Y)(p22 .3;p11 .3)(DXZ1
+,DYZ3+,SRY+,KAL+,telXp-/Yp-) . The second case reared as a female
and had right testis, a uterus and left ovary with some follicles .
The karyotype was 45,X/46,X,+mar.ish idic(Y)(qter→p11.3::p11.3→
qter)(wcpY+,DYZ3++,SRY+,telYp-) .The 1 st case diagnosed as mixed
gonadal dysgenesis and the second as true hermaphroditism .To our
knowledge this is the 1st case of true hermaphroditism with this distal
break points . The other 4 cases presented with primary amenorrhea
and short stature . Karyotype of 3 rd case was 45,X/46,X,+mar .
ish idic(Y)(pter→q11::q11→pter)(DYZ3++,SRY++).The 4 th case had
46,X,der(X) ish. Der(X)(pter→q21::p22.1→pter)(DXZ1+,XIST+,telXp+
+,STS++), the 5 th case had severe short stature and her karyotype was
46,X,der(X). ish der(X)(qter→p11.2::p11.2→qter)(wcp X+, DXZ1++).
The 6 th case had 46,X,der(X).ish idic(X)(pter→q25::q25→pter)(wcpX
+DXZ1++,XIST++,telXp++) .
A team of specialists collaborated together to give the proper genetic
counseling and follow-up specially for cases with Y chromosome who
had the risk of gonadoblastoma .We recommend further investigations
using Array CGH for identification of duplication / deletion in different
regions of sex chromosomes .
P02.197
molecular cytogenetic characterization of a small supernumerary
marker chromosome derived from chromosome 11 in a mother
and a child with distinct phenotypes
J. B. Melo 1 , E. Matoso 1 , M. R. Lima 2 , L. Backx 3 , J. R. Vermeesch 3 , N. Kosyakova
4 , T. Liehr 4 , I. M. Carreira 1 ;
1 Laboratório de Citogenética and Centro de Neurociências e Biologia Celular,
Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal, 2 Instituto
Genética Médica Jacinto Magalhães, Porto, Portugal, 3 Center for Human Genetics,
University Hospital Leuven, Leuven, Belgium, 4 Institut für Humangenetik
und Anthropologie, Jena, Germany.
Small supernumerary marker chromosomes (sSMC) are defined as
structurally abnormal chromosomes that cannot be identified or characterized
unambiguously by conventional banding cytogenetics alone,
and are generally equal in size or smaller than a chromosome 20 of
the same metaphase spread . sSMC derived from chromosome 11 are
rare and, so far, it is not yet clear which regions of chromosome 11 are
critical and have clinical consequences .
We report a mother and a child with a karyotype 47,XX,+mar[21]/
46,XX[9] and 47,XY,+mar[25]/46,XY[5], respectively . After centromeric
FISH the origin of the sSMC was ascertained as derived from chromosome
11 . Subcentromeric FISH revealed the presence of two different
shapes of the sSMC in the mother, with apparently the following
breakpoints - ish r(11)(::p11 .12~11 .2->q12::)[2]/min(11)(p:11 .12~11 .2-
>q12:)[7]; and three different shapes of the sSMC in the child
- ish r(11)(::p11 .12~11 .2->q12::)[6]/r(11;11)(::p11 .12~11 .2->q12::
p11 .12~11 .2->q12::)[3]/min(11)(p:11 .12~11 .2->q12:)[4] . The sSMC
was microdissected and amplified by DOP-PCR. The amplified DNA
was analysed by array painting, using fulltilling array specific for chromosome
11 (with 100-150 kB resolution) . An unexpected result revealed
an unusual sSMC . A maternal uniparental dissomy of chromosome
11 was excluded . The child presents a more severe phenotype,
with facial dysmorphisms, strabism, ptosis, mental retardation and
developmental delay . The mother has a congenital cardiopathy and no
apparent mental retardation .
Molecular cytogenetics techniques are a valuable tool for the accurate
identification of the genetic origin and content of sSMC, contributing to
a better genotyphe/phenotype correlation .
Supported in parts by the Erwin-Riesch Stiftung.
P02.198
three de novo deletions, one transposition, and one inversion of
chromosome 6 in a patient with complete absence of expressive
speech and reduced pain perception
M. Poot 1 , R. van ‘t Slot 1 , R. Leupert 2 , V. Beyer 2 , E. Passarge 3 , T. Haaf 2 ;
1 Department of Medical Genetics, Utrecht, The Netherlands, 2 Institut für
Humangenetik, Johannes Gutenberg-Universität Mainz, Mainz, Germany, 3 Institut
für Humangenetik, Universitätsklinikum Essen, Essen, Germany.
Using the Infinium HumanHap300 Genotyping BeadChip SNP array
and BAC-based FISH we found three adjacent, but non-contiguous
de novo deletions, one transposition and one pericentric inversion of a
chromosome 6 in a patient whose karyotype was previously described
by banding analysis as 46,XX,del(6)(q13q15),inv(6)(p11 .2q15) . In addition
to the deletion of band 6q14 detected previously by classic cytogenetics,
we found two additional microdeletions . The most distal
one is a 360 kb deletion in band 6p12 .3, containing the genes RHAG,
CRISP1, 2, and 3, and PGK2 . The second deletion in 6p12 .2-p12 .1,
containing the genes PKHD1, IL17, MCM3, EFHC1, and TRAM2
genes is 1 .15 Mb in size . The deletion in region 6q14 .3-q16 .1, reported
previously, was mapped more precisely and determined to be 11 .9
Mb in size . It contains 27 genes, some of which are involved in pain
sensation, growth regulation, and tissue modeling during development.
The refined karyotype is 46,XX,der(6)(pter◊p12.3::p12.1◊p12.1::
q14.3◊p12.1::p12.3◊p12.2::q16.1◊qter) or (pter◊p12.3::p12.1◊p12.1::
q14.3◊p12.1::p12.2◊p12.3::q16.1◊qter).The main clinical features of
this 31-year-old women are dysmorphic facial features consisting of
a broad face, prominent glabella, broad nose, and hypertelorism, nonprogressive
deficit of motor control, in particular a broad-based slowmotion-like
gait, absence of speech development, inability to acquire
and to comprehend theoretical knowledge, and reduced sensitivity to
pain . The rearrangement of chromosome 6 presumably originated in
a paternal meiosis . By combining the SNP array and FISH data we
were able to completely map and to reconstruct this highly complex
rearrangement in a single chromosome .
P02.199
characterization of a small supernumerary marker
chromosomes using cytogenetic and molecular cytogenetic
methods (two case reports)
M. Miskovic 1 , T. Liehr 2 , M. Guc-Scekic 1,3 , A. Weise 2 , K. Mrasek 2 , T. Lalic 1 , N.
Lakic 1 ;
1 Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade,
Serbia, 2 Institute of Human Genetics and Anthropology, Jena, Germany, 3 Faculty
of Biology, University of Belgrade, Belgrade, Serbia.
Small supernumerary marker chromosomes(sSMC),defined as additional
abnormal chromosomes, too small for characterization by
conventional banding cytogenetics alone,are present in 0 .043% of
newborns and 0 .077% of prenatal cases .About 1/3 of the sSMC are
correlated with a specific clinical picture,while most of the remaining
sSMC have not yet been associated with clinical syndromes .
We present two cases with sSMC in karyotype which were initially
studied by GTG banding technique.To define origin of sSMC,additional
molecular cytogenetic methods (FISH) were performed using probe
sets:cenM-FISH and subcenM-FISH Mix for the corresponding chromosomes
.
Patient 1 had a diagnosis of total anomalous pulmonary venous return
and facial dysmorphism .Here a mosaic karyotype 47,XX,+mar[22]/
46,XX[11] was detected .The sSMC was characterized as an
invdup(22)(q11 .21) .Similar cases were previously reported and the
patient could now clinically be diagnosed as having a Cat-Eye syndrome
.
Patient 2 was a prenatal diagnosis of 42-years old woman with fetal
karyotype 47,XY,+mar(de novo) .In this case sSMC was characterized
as an invdup(15)(q11 .1) .According to the literature similar cases didn’t
show any clinical abnormalities .This type of sSMC is the most common
(appears with 30% frequency) .
It is difficult to predict precisely the phenotypic risk that could be associated
with the presence of sSMC .The origin of sSMC is important
factor in determining its possible phenotypic effect .Conventional cytogenetic
techniques are limited .Molecular cytogenetic methods are
necessary in terms of providing the information about marker origin
and structure .It’s only way to establish phenotype-karyotype correlation
and discuss the results in genetic counseling .
Acknowledgments:Supported in parts by the DFG (436RUS17/135/
03;436RUS17/109/04,436RUS17/22/06),Boehringer Ingelheim Fonds
and the Evangelische Studienwerk e .V .Villigst .
P02.200
the Effect of chromosomal Rearrangements on Gene
Expression
A. Reymond 1 , F. Schütz 1 , J. Chrast 1 , M. Delorenzi 1 , W. A. Bickmore 2 , L. A. J.
Harewood 1 ;
1 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzer-