2009 Vienna - European Society of Human Genetics

Cytogenetics
were normal. CGH array was performed and revealed a duplication of
the 11p11-q13 region. This was then confirmed by FISH.
BAC-CGH array and BAC probes (FISH) allowed the determination
of the precise localization of the breakpoints in our patient. Cromosome
11 genes located in this region may play a critical role in brain
development.
P03.132
FisH probe selection for preimplantation genetic diagnosis in
couples with reciprocal translocation
J. C. Wang, R. Habibian, J. Szymanska, A. Hajianpour;
Genzyme Genetics, Monrovia, CA, United States.
Individuals with balanced reciprocal translocations are at risk for adverse
pregnancy outcomes due to aberrant meiotic segregation. Performing
PGD by interphase FISH can decrease the risk by selectively
transferring only normal or balanced embryos. We show that as long
as one subtelomere probe for FISH analysis is targeted at one of the
two translocation segments, the second subtelomere probe can be directed
to any of the remaining three subtelomeres. In combination with
an appropriately selected centromeric probe, the tri-color probe set
can detect all unbalanced segregants. The feasibility of using subtelomeric
probes other than those for the two translocated segments has
practical value; if one probe is unavailable or if the signal is suboptimal,
an alternate probe can be substituted. When centromeric probe
in a third color is not available, a two-hybridization protocol performed
sequentially will be necessary to detect all unbalanced segregants.
This is achieved by using dual-color short and long arm subtelomere
probes of one chromosome followed by a second hybridization with
the subtelomere probes of the other chromosome.
This general guideline cannot be applied to two types of reciprocal
translocations: cases with centromere break and cases in which the
breakpoint is distal to the available subtelomere probe. The interphase
FISH signal pattern in such cases cannot be predicted by examining
the karyotype alone. It is therefore imperative that pre-PGD interphase
and metaphase FISH analyses be performed on all translocation carriers
to confirm that probes selected for PGD are appropriate. Examples
of such cases will also be presented.
P03.133
cytogenetic investigation of an intersticial deletion 4q de novo
and Rieger anomaly: a case report
N. Oliva-Teles1 , C. Candeias1 , B. Marques1 , J. Silva1 , G. Soares1 , S. Gonçalves2
, H. Correia1 ;
1INSA, I.P., Centro de Genética Médica Jacinto Magalhães, Porto, Portugal,
2Centro Hospitalar do Porto, Porto, Portugal.
Interstitial deletions of the long arm of chromosome 4 involving the
region 4q25-q27 are rare occurrences. The clinical features of patients
carrying similar deletions include craniofacial and skeletal anomalies,
malformations of the eye, cardiac abnormalities and developmental
delay. Rieger Syndrome (RS) (OMIM #180500) is an autosomal dominant
disorder that conditions an abnormal eye development which
results in blindness from glaucoma in approximately 50% of affected
individuals (gene map locus 4q25-q26). We report on a male child
aged 4 presenting with development delay, attention deficit/hyperactivity,
normal growth, Rieger anomaly, small conical teeth and some
mild dysmorphic features. Classical karyotyping using high resolution
GTG banding revealed a de novo 4q (?q25?q27) interstitial deletion.
To define the deletion breakpoints and the extent of the deletion, CGH
techniques and FISH analysis using BAC DNA and are in progress.
The authors enhance the importance of high resolution banding for
detecting subtle chromosome 4q deletions in patients with phenotypic
characteristics of Rieger syndrome and compare the present case
findings with previously published data.
P03.134
De novo mosaic of ring chromosome 3: a new case with growth
retardation
M. Pilechian Langeroudi, C. Azimi, F. Farzanfar, M. Khaleghian;
Department of Genetics, Cancer Institute, Imam Khomeini Hospital Complex,
Tehran University of Medical Sciences, Islamic Republic of Iran.
There are only a few published cases of ring chromosome 3. This is
the first report from Iran about a girl with a de novo mosaic of ring
cnromosome 3. Our case was the first child of healthy, non-consan-
guineous parents. The maternal age was 26 years and paternal age
was 33 years at delivery. There was no problem during the pregnancy.
She was born with Cesarean section at full term and there were no
neonatal complications. Her birth weight was 2480 g, her height was
44 cm and her OFC was 29.5 cm. Our case was referred to our department
due to growth retardation. She was 3.5 years old ; her weight
was 9200 g, height was 87 cm and OFC was 43 cm. Her face was
triangular, with small chin, mild retrognathia and her palpebral fissures
were slanted upward and outward. There was telecanthus, small alae
nasi with a full nasal tip, and normally positioned, simple ears.The first
two toes were widely spaced bilaterally. Her eyes, hearing, talking and
IQ were normal. Karyotyping was performed on her peripheral blood.
Heparinized blood samples were cultured, harvested and banded according
to standard methods.
Her karyotype showed:
mos46,XX,r(3)(p26 q29) [70] / 45,X,-3 [4] / 46,XX,dic r(3;3)(p26
q29;p26 q29) [1]
Chromosomal studies of her parents were normal.
P03.135
Clinical findings and cytogenetic analysis of a ring chromosome
7 in a girl referred for suspicion of Fanconi Anaemia
A. Amouri 1,2 , W. Ayed 1 , R. Bhouri 1 , I. El Kamel - Lebbi 1 , O. Kilani 1 , H. Guermani
1 , N. Abidli 1 , F. Talmoudi 1 , S. Abdelhak 2 , N. Bouayed-Abdelmoula 3 ;
1 Cytogenetic Laboratory, Pasteur Institute, Tunis, Tunisia, 2 Molecular Investigation
of Genetic Orphan Diseases Research Unit (MIGOD), UR26/04, Pasteur
Insitute of Tunis, Tunis, Tunisia, 3 Laboartoire d’Histologie Embryologie, Faculté
de Médecine de Sfax, Tunis, Tunisia.
Ring chromosome 7 is a rare but well documented chromosomal aberration
in man. So far at least 18 cases have been reported in the literature
showing a variable but distinct pattern of phenotypic characteristics
in affected individuals. Besides others, skin findings as pigmented
naevi are especially frequent.
We report on a girl with mosaicism of a de novo ring chromosome 7.
She presented for bicytopenia and was suspected for Fanconi Anemia.
The main clinical features were growth failure, cafe-au lait spots and
multiple pigmented naevi. Psychomotor development was normal and
no major malformations were present. Chromosome analysis after R
banding and FISH showed a big ring chromosome 7 in 90% of consecutively
scored metaphases (46,XX,r(7)/45,XX,-7/46,XX). The medullar
karyotype showed a monosomy 7.
We reviewed previously reported patients with ring chromosome 7 in
an attempt to establish genotype-phenotype correlations, which are
particularly important for genetic counselling and clinical genetics. Our
patient may represent the first case of ring chromosome 7 with haematological
manifestation.
P03.136
clinical, cytogenetic and molecular characterization of ring
chromosome 9 formation due to inverted duplication and
terminal deletion
L. Morozin Pohovski, I. Sansovic, I. Barisic, I. Petkovic;
Children’s University Hospital Zagreb, Zagreb, Croatia.
Ring chromosome 9 is a rare chromosome aberration associated with
variable phenotype that may include growth and psychomotor retardation,
microcephaly, dysmorphic facial features, heart malformation,
ambiguous genitalia, limb and skeletal defects. The majority of ring (9)
cases arise from deletions of the chromosome with breakpoint positions
between 9p22-9p24 and 9q33-q34, followed by the fusion of the
ends of terminal segments. Very rarely other structural aberrations are
involved. Here we describe a XY sex-reversed patient carrying ring
chromosome 9 with additional material on 9p. High resolution banding
suggested the presence of a duplication of band p23. Fluorescent
in situ hybridization (FISH) analysis with whole chromosome painting
probe for chromosome 9 excluded an insertion or a translocation from
other chromosomes. The analysis with TelVision 9p and 9q probes
identified the subtelomere - specific sequences on 9q but failed to
detect a hybridization signal on 9p. The breakpoint positions and the
size and location of duplication were further analyzed by molecular
techniques using microsatellite DNA markers and multiplex ligation
dependent probe amplification (MLPA). The karyotype was designated
as 46,XY,r(9)(p24;q34.3)inv dup(9)(p24p22)mat. From 24 cases of
ring (9) reported so far, there is only one case which included distal
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