2008 Barcelona - European Society of Human Genetics

Cytogenetics
P02.082
Phenotype and 244k array-cGH characterization of chromosome
13q deletions: An Update of the Phenotypic map
M. Stefanova 1,2 , R. Stoeva 3 , A. Bisgaard 1 , B. Dimitrov 4 , G. Gillessen-Kaesbach
5 , J. Fryns 4 , H. Rose 1 , L. Grozdanova 3 , I. Ivanov 3 , K. Keymolen 2 , C. Fagerberg
6 , L. Tranebjaerg 7,8 , M. Kirchhoff 1 ;
1 Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 2 Center
for Human Genetics, Free Flamish University Hospital, Brussels, Belgium,
3 Medical University, Plovdiv, Bulgaria, 4 Center for Human Genetics, University
of Leuven, Leuven, Belgium, 5 Institute of Human Genetics, Campus Lubeck,
Schleswig-Holstein University Hospital, Lubeck, Germany, 6 Department of
Clinical Genetics, Vejle Hospital, Vejle, Denmark, 7 Department of Audiology,
Bispebjerg Hospital, Copenhagen, Denmark, 8 Wilhelm Johannsen Centre for
Functional Genomics, Institute of Cellular and Molecular Medicine, The Panum
Institute, Copenhagen, Denmark.
Genotype-phenotype correlation studies of partial deletions of the long
arm of chromosome 13 have been reported previously, each focusing
on few particular major anomalies, such as brain, eyes, inner organs,
hands and feet, genitourinary or anorectal defects . Chromosome
regions critical for some of the major malformations, however, vary
noticeably and await precise delineation . Besides, data about the dysmorphic
profile are limited. In order to update the phenotypic map for
chromosome 13q deletions, we applied high resolution 60-mer oligonucleotide-based
microarray containing 244 .000 probes with a median
spacing of 7 .4 kb to 16 .5 kb (Agilent Technologies, USA) to determine
the exact breakpoints of such deletions in 14 patients . We linked the
genotype to the patient’s phenotype and were able to refine the smallest
deletion region linked to microcephaly (13q33 .3-q34), Dandy-Walker
malformation (DWM) (13q32 .2-q33 .1), corpus callosum agenesis
(CCA) (13q32 .3-q33 .1), the associated occurrence of both DWM/CCA
(13q32 .2-q33 .1), meningocele/encephalocele (13q31 .3-qter), ano-/microphthalmia
(13q31 .3-13qter), cleft lip/palate (13q31 .3-13q33 .1), lung
hypoplasia (13q31 .3 - 13q33 .1), anal atresia/hypospadias/penoscrotal
inversion (13q33 .1-13q34), thumb a-/hypoplasia (13q31 .3-q33 .1
and 13q33 .3-34) . ‘Typical’ 13q-dysmorphic facial features were assigned
along the chromosome, thereby mapping, the prominent nasal
columella between 13q31 .3 and 13q33 .3 . Our analyses support the
hypothesis that haploinsufficiency of more than one locus within the
13q21 .1-qter region is responsible for brain anomalies and neural tube
defects . In contrast to previous reports of carriers of 13q32 band deletion
as the most seriously affected patients, we present such individuals
with a long-term survival .
P02.083
clinical features of a case with trisomy 10q and monosomy 3p
resulting from a maternal balance translocation: A case report
and review of clinical features
F. Mahjoubi 1,2 , M. Akbary 3 , S. Karemee 4 , G. Babanohammadi 4 ;
1 NIGEB, Tehran, Islamic Republic of Iran, 2 3Tehran Medical Genetic Laboratory,
Taleganee St, Tehran, Iran,, Tehran, Islamic Republic of Iran, 3 Medical Genetic
Dept., Tarbiat Modaress University, Tehran, Iran, Tehran, Iran (Islamic Republic
of, Tehran, Islamic Republic of Iran, 4 3Tehran Medical Genetic Laboratory, Taleganee
St, Tehran, Islamic Republic of Iran.
Here we describe clinical and cytogenteic data on 2 year female child
with partial trisomy for the distal part of the long arm of chromosome
10 (10q22-->qter) and a concomitant monosomy 3(p25-->pter) as a
result of a maternal balanced reciprocal translocation . Her karyotype
was ascertained as 46,XX,der(3)t(3;10)(p25;q22) . The father had normal
karyotype . The mother had an apparently balanced translocation
involving chromosome 3 and 10 [46,XX,t(3;10)(p25;q22)] . To our best
knowledge, this is the second reported case of partial trisomy 10q and
partial trisomy 3p and first reported case from Iran. Clinical features of
this case and a few published cases will be reviewed briefly.
P02.084
trisomy 13 mosaicism in a nine-year-old girl with mild global
developmental delay
L. E. Kim;
McMaster University Medical Centre, Hamilton, ON, Canada.
Trisomy 13 is associated with mental retardation and a variety of congenital
abnormalities . Survival past infancy is rare because of the lifethreatening
medical issues associated with this condition . The phenotype
of mosaic trisomy 13 is extremely variable . I report on a nine-
year-old girl who was found to have trisomy 13 mosaicism at the age
of eight in the course of investigations for mild global developmental
delay . She was born after an unremarkable pregnancy and delivery .
Her parents first became concerned when she was two-years-old because
her fine motor and speech milestones were delayed. Currently,
she is integrated into a regular grade three class where she receives
some remedial help; a recent developmental assessment revealed
that she is functioning at the level of a six-year-old . She also has
some gross motor difficulties and decreased coordination. Her general
health has been good . Examination revealed that her weight and
height were >97 th percentile and that her head circumference was at
the 80 th percentile . Her facial features were slightly coarse . There was
no other evidence on examination of any physical features associated
with trisomy 13 . The patient’s karyotype was done on a blood sample
and revealed that 10 out of 20 cells analyzed were trisomic for chromosome
13 (ie . 50%) . This case supports the previously suggested idea
that the percentage of trisomic cells, which is thought to decrease with
age, correlates poorly with intellectual functioning .
P02.085
Detection of Y chromosome and trisomy 8 mosaicism in a twelve
year old girl with turner syndrome
K. Koronioti1 , P. Apostolopoulos2 , A. V. Divane1 ;
1Department of Cytogenetics, Locus Medicus, Diagnostic Centre, Athens,
Greece, 2In Vitro, Diagnostic Laboratory, Athens, Greece.
Most Turner syndrome (TS) patients show no evidence of Y chromosome
sequences . According to different authors some TS patients
may have Y chromosome material present in a few cells that are not
detected by standard cytogenetic analysis. The rationale of identification
of this low level mosaicism is of clinical importance due to the
patient’s increased risk of developing gonadoblastoma .
Here we report conventional and molecular cytogenetic investigations
in a case of mosaic sex chromosome aneuploidy combined with mosaic
trisomy 8 and the presence of low level Y mosaicism . A 12 year-old
girl was presented with short stature, gonadal dysgenesis and minor
craniofacial dysmorphic features .
Standard chromosome analysis on peripheral blood lymphocytes
showed the presence of three cell lines, whose karyotypes were 45,X
[93%], 47,XY,+8 [5%] and 46,XX [2%] . FISH analysis was performed
using as probes an alpha satellite for X chromosome (CEPX, Xp11 .1q11
.1), a satellite III for Y chromosome (CEPY, Yq12) and an alpha
satelitte for chromosome 8 (CEP 8, 8p11 .1-q11 .1) . The results of FISH
analysis were in concordance with those of conventional cytogenetic
analysis showing a slight increase in the percentage of interphase
nuclei revealing trisomy 8 and Y chromosome mosaicism (8% FISH
versus 5% standard cytogenetics) .
The importance of systematic search for hidden Y chromosome mosaicism
in patients with TS is justified by the possibility of developing
gonadoblastoma and it is necessary for the appropriate clinical management
of the patient .
P02.086
isolated bilateral Ulnar Agenesis due to 4q34.1 deletion in a
young male patient
S. Manouvrier-Hanu 1,2 , M. Holder-Espinasse 1,3 , B. Maisonneuve 4 , A. Mezel 5 , B.
Herbaux 6,3 , F. Escande 7 , J. Kerckaert 8 , J. Andrieux 9 ;
1 Génétique clinique, CHRU, Lille, France, 2 faculté de médecine, Université Lille
2, Lille, France, 3 Faculté de médecine, Université Lille 2, Lille, France, 4 Centre
de rééduccation Marc sautelet, Villeneuve d’Ascq, France, 5 Service de chirugie
et orthopédie de l’enfant, CHRU, Lille, France, 6 service de chirurgie et orthopédie
de l’enfant, CHRU, Lille, France, 7 Génétique moléculaire, CHRU, Lille,
France, 8 plateforme de génomique, Lille, France, 9 Plateforme de génomique,
CHRU, Lille, France.
Ulna a- or hypo-plasia is a rare condition, mostly occurring associated
with other malformations as in Schinzel-Ulnar-Mammary, Weyers, or
Femur-Fibula-Ulna syndromes . If isolated the disease is very uncommon
and, to our knowledge, remains unexplained . We describe a 3
years old male patient with bilateral isolated ulna aplasia and 4q34 .1
deletion diagnosed by Array-CGH .
This patient was the first child of young, healthy and non consanguineous
parents . He had a healthy young sister . The pregnancy was uneventful
. He was born at term . He had aplasia of both ulnas with bilateral
but asymmetrical absence of post-axial rays . Only the thumb was