2008 Barcelona - European Society of Human Genetics

Cytogenetics
P02.091
Identification of a rare cytogenetic aberration of chromosome 5
identified by fluorescent in situ hybridization
L. Losonczi, M. Dobos, J. Szabó, J. Szabolcs, T. Bense, G. Fekete;
2nd Department of Pediatrics, Budapest, Hungary.
Introduction: We report a rare cytogenetic aberration of chromosome
5 .
Case report: Our patient, after delivered from second, with polyhydramnion
complicated pregnancy, had bradycardia and cyanosis . His
gestational age was 39 weeks, and the birthweight was 2910 grams .
After delivery he had to be ventilated for some minutes . He got antibiotics
because of perinatal infection . During feeding he became cyanotic
. Echocardiography revealed 10 mm wide second type atrial septal
defect . Neurological investigations revealed generalized hypotonia .
Other characteristic finding was the baby’s strange crying. Some minor
anomalities could be detected, such as low and back sitting ears,
short palpebral fissure, abnormal shape of the cranium, and clubbed
fingers. In the family-history was no abnormality. Because of minor abnormalities
and congenital heart defect cytogenetic investigations was
done . The cytogenetic investigation with G bands and FISH revealed
the duplication of the cri du chat region [46,XY,dup(5)(p15 .2 p15 .3)] .
Parents’ karyogram was normal . This type of cytogenetic abormality
of chromosome 5 is rare, 9 cases have been reported until now, with
similar clinical and cytogenetic findings. The feeding of the infant was
difficult, suffered often from infections, had failure to thrive. Because of
the wide ASD the cardiac function became worse, severe pulmonary
hypertonia developed . He died at the age of 6 months, with symptoms
of circulatory insufficienty.Conclusion: A rare cytogenetic aberration of
chromosome 5 is described, which help to understand the genotypephenotype
correlation in patients with 5p duplication .
P02.092
A submicroscopic 5q11.2 deletion in a girl with autism, mild
mental retardation and mild facial dysmorphism
H. Peeters 1 , A. Crepel 1 , K. Devriendt 1 , P. De Cock 2 , J. Vermeesch 1 , J. P. Fryns 1 ;
1 University of Leuven, Center for Human Genetics, B-3000 Leuven, Belgium,
2 University of Leuven, Child Neurology Department, B-3000 Leuven, Belgium.
We report on a female patient with autism spectrum disorder (ASD),
mild mental retardation, mild facial dysmorphism and a submicroscopic
5q11 .2 deletion detected by 1-Mb array CGH . In addition, a 2Mb
maternally inherited duplication on Xp22 .31 (RP11-483M24->RP11-
323F16) was detected . Chromosomal imbalances (deletions or duplications)
appear to be present in about 25% of patients with syndromic
ASD . The deletion in the present patient is approximately 8 Mb in size
and is flanked by the clones CTD-2276024 and RP11-210O14. Interestingly,
a similar but possibly slightly smaller deletion on has previously
been described in a boy with profound speech delay, obsessional
play and echolalia (K Prescott et al. 2005) . In contrast to the
patient we describe, this boy presented additional malformations like a
cardiac defect (tetralogy of Fallot), a bifid uvula, velopharyngeal insufficiency
and short stature . Since autistic behaviour is the only consistent
finding in 2 patients with a similar deletion 5q11.2, the location of this
deletion may identify a gene that is implicated in autism spectrum disorders
. Furthermore our observation illustrates that array-CGH should
be considered as an essential aspect in the genetic analysis of patients
with syndromic ASD .
P02.093
Non acrocentrics ssmc: thirteen new cases
M. Santos, A. Escalona, C. Hernando, C. Fuster;
Universitat Autonoma de Barcelona, Bellaterra, Spain.
Context Small supernumerary marker chromosomes (sSMC) are common
findings in Prenatal and Postnatal Diagnosis. So far, the genetic
origin of these sSMC usually remained unknown . Recently the use of
several technologies based on FISH has allowed an important progress
toward this goal .
Objective To characterise 50 sSMC detected in unrelated patients with
constitutional genetic disorders, mental retardation or infertility .
Methodology G-banding, HR-CGH and FISH (M-FISH, BACs)
Results Acrocentric sSMC were detected in 74% (37/50) of cases .
Inv dup(15) was the most commonly detected sSMC followed by inv
dup(13 or 21) . Non acrocentric sSMC were detected in the rest of cases
(26%, 13/50) . sSMC derived from chromosomes 2, 3, 4, 7, 8, 9, 11, 17,
18 (three cases), 20 and X were also identified and two of them were
neocèntric (those derived from chromosomes 3 and 20) . In two cases,
we detected at least 4 sSMC derived from the same chromosome but
with different morphologies . In one they derived from chromosome
9 and in the other they derived from chromosome X . In general, we
found according with the literature that the presence of euchromatin in
the de novo sSMC is linked with an abnormal phenotype .
Conclusion The use of combined molecular cytogenetic techniques revealed
that the incidence of non acrocentric sSMC is probably higher
than expected .
ACKNOWLEDGMENTS: This work was supported by MCYT (SAF
2003-03894) and CIRIT (2005, SGR-00495) and Generalitat de Catalunya
(Grant 2002FI00281)
P02.094
Familial chromosomal rearrangement with an extra micro
derivative 22 compensating a 22q11.2 deletion
J. Nevado 1,2 , M. A. Mori 1,2 , L. Fernández 1,2 , P. D. Lapunzina 1,2 , B. Garcia 3 , M. L.
De Torres 1,2 ;
1 Hospital Universitario la Paz, Genética Médica, MADRID, Spain, 2 CIBERER,
Madrid, Spain, 3 Hospital Universitario Príncipe de Asturias, Bioquímica Clínica,
Unidad de Genética, Alcalá de Henares (MADRID), Spain.
We described a non-consanguineous couple (33 year-old) that underwent
amniocentesis for prenatal cytogenetic studies (in the 15 th gestational
week) due to the man is carrying an unusual rearrangement with
an extra micro-chromosome, which renders a high probability to have
cases of 22q11 .2 deletion syndrome in the family . His karyotype is: 46,
XY [22%] /47, XY, + mar [78%] . ish del (22) (q11 .2 q11 .2) (D22S987E-
D22S976E-)/ ish del (22) (q11 .2 q11 .2) (D22S987E-D22S976E-), +
mar . ish der (22) (D22S987E-D22S976E+) .
The prenatal cytogenetic study, including FISH, in amniotic fluid (43
cells studied from three independent cell cultures) and cord blood (100
cells studied) showed a deletion in region 22q11 .2: 46, XY . ish del (22)
(q11 .2 q11 .2) (D22S987E-D22S976E-) . No trace of an extra microchromosome
was found . In the Genetic counselling clinics the couple
was told about the consequences of 22q11 .2 deletion syndrome and
they decided termination of the pregnancy .
An important remark in this family is that, members who are carrying
the extra chromosome are phenotypically normal because they are
chromosomically balanced at this region . Thus, it must be important to
rule out the 22q11 .2 deletion, using FISH and/or MLPA, in members of
the family with apparently normal number of chromosomes .
P02.095
Autistic features with speech delay in a girl with an ~1.5 mb
deletion in 6q16.1, including FUt9 and GPR63
K. W. Derwinska1,2 , J. Bernaciak1 , E. Obersztyn1 , E. Bocian1 , P. Stankiewicz1,2 ;
1 2 Institute of Mother and Child, Warsaw, Poland, Dept. of Molecular & Human
Genetics, Baylor College of Medicine, Houston, TX, United States.
Recent studies have shown that up to 40% of the apparently balanced
reciprocal chromosome translocations in patients with abnormal phenotype
can be accompanied by a chromosome imbalance . We present
a 10-year-old girl with mild mental retardation, abnormal EEG, and autistic
behavior, who began to speak at 5 years . She had no dysmorphic
features and her brain MRI was normal . Karyotype analysis revealed
a de novo apparently balanced translocation t(6;14)(q16;q22) . Whole
genome array CGH analysis with ~385,000 oligonucleotide probes
(NimbleGen) identified an ~1.48 Mb deletion in 6q16.1. FISH with
BAC clones mapping within and directly flanking the deleted segment
showed that the deletion arose at the translocation breakpoint . Interestingly,
autism has been linked previously to chromosome 6q16 . The
deleted segment harbors FUT9, GPR63, FHL5, KLHL32, c6orf66, and
AK091365 and two predicted genes c6orf167 and KIA0776 . GPR63
is expressed almost exclusively in the brain and encodes a G-protein-coupled
receptor for sphingosine 1-phosphate . The fucosyltransferase
9 gene, FUT9, is highly conserved among humans, mice, rats,
and hamsters and is highly expressed in brain during embryogenesis .
FUT9 is considered to be involved in cell-cell interactions, differentiation,
and neurodevelopmental processes. Our data confirm previous
observations that copy-number variation is a significant factor responsible
for autistic spectrum behavior and speech delay .