2008 Barcelona - European Society of Human Genetics

Cytogenetics
netic map of deleted region and clinical features are now discussed .
In all cases of del(22)(q11), suspected with negative results of typical
cytogenetic analyses, possibility of subtle aberrations of 4q terminal
region must be carefully considered .
P02.133
interstitial deletion of the long arm of the chromosome 10: about
a tunisian case with del(10)(q23q25)
l. ben jemaa, l. kraoua, r. meddeb, m. chaabouni, f. maazoul, r. mrad, h. chaabouni;
service des maladies congénitales et héréditaires, tunis, Tunisia.
We describe a Tunisian patient, a one month-old boy wich is the second
child of healthy unrelated parents . During pregnancy there was
intra-uterine delay of growth .
The infant was premature and was born at 35 weeks of pregnancy .
Birth weight was 1850 g, length was 49 cm, and head circumference
was 33 cm .
There was a facial dysmorphism consisting of down slanting palpebral
fissures, prominent forehead, broad nasal bridge, anteverted nares,
thin lips, high palate, low-set ears, long philtrum and retrognathia . He
had short neck, clinodactyly of the fifth fingers, a unique left kidney,
shawl scrotum and club foot varus .
The cytogenetic analysis revealed deletion of the long arm of chromosome
10: 46,XY,del(10)(q23q25) in all mitosis . His parents showed
normal karyotypes .
Interstitial deletions of 10q are rare, this report describes a boy with a
de novo interstitial deletion of the long arm of chromosome 10 . Typical
presentation includes craniofacial dysmorphisms, postnatal growth
retardation, digital anomalies, developmental delay, congenital heart
defects and urogenital anomalies. The clinical findings are mainly
the same as those reported in patients with interstitial deletion of this
region especially facial dysmorphism, our patient has no congenital
heart defect, why he has unique left kidney and most of the patients
described have a deletion more distal than our deletion .
The breakpoint will be confirmed by FISH analysis and well permit to
compare exactly the phenotype in this case with those described in
litterature were there is only few cases of this deletion .
P02.134
Deletion (1)(p32.2-p32.3) detected by Array-cGH in a Patient with
Developmental Delay/Mental Retardation, Dysmorphic Features
and Low cholesterol: A New microdeletion syndrome?
F. Quintero-Rivera 1 , T. P. Leren 2 , J. Llerena 3,4 , N. Rao 1 , M. Mulatinho 3,1 ;
1 David Geffen School of Medicine at UCLA, Department of Pathology and
Laboratory Medicine, Los Angeles, CA, United States, 2 Medical Genetics Laboratory,
Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical
Center, Oslo, Norway, 3 Universidade Federal do Rio de Janeiro, UFRJ, Rio
de Janeiro, Brazil, 4 Instituto Fernandes Figueira, IFF/FIOCRUZ, Rio de Janeiro,
Brazil.
We report a 25-year-old male with developmental delay/mental retardation,
low levels of total and LDL cholesterol and dysmorphism, which
includes macrocephaly, hypertelorism, downslanting palpebral fissures,
low set ears, bilateral cataracts, cleft palate, bilateral cleft lip and wide
spaced nipples . While his karyotype and subtelomeric FISH studies
were normal, a 5 .4 Mb interstitial deletion at 1p32 [del(1)(p32 .2-p32 .3)]
was identified by array-CGH. This region encompasses a cluster of
genes involved in fatty acid oxidation and cholesterol metabolism . One
of these genes is PCSK9 (proprotein convertase subtilisin/kexin type
9), which is a key regulator of the number of cell-surface LDL receptors .
Another gene deleted is , DAB1 (Disabled 1 homolog of Drosophila),
which is involved in brain development. Based on the findings in our
patient and in the two previously reported individuals with del(1)(p32 .2p32
.3), they may have a new microdeletion syndrome that previously
has been difficult to detect by G-banding because it is located in a Gnegative
band, but it can easily be identified by array-CGH
P02.135
Identification of a 2.7 Mb deletion of 3q25.1-3q25.2 in a patient
with complex rearrangements of chromosome 3 by oligo-array
cGH
E. Seo, J. Lee, H. Yoo, I. Park;
University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic
of Korea.
Interstitial deletion of chromosome 3q23 is known in blepharophimosis-ptosis-epicanthus
inversus syndrome (BPES) . Recently, a 1 .9 Mb
deletion of 3q24 haboring ZIC1 and ZIC4 has been identified in Dandy-Walker
malformation . We present a Korean boy with mild dysmorphism
and congenital heart disease such as pulmonary atresia, VSD
and major aortopulmonary collateral artery (MAPCA) at birth . He had a
apparently balanced translocation, 46,XY,der(3)inv(3)(p25q25)t(3;8)(q
29;q24 .1),der(8)t(3;8) de novo, with complex rearrangements of chromosome
3 . A high density array CGH with 244k oligonucleotide probes
detected a 2 .7 Mb deletion at 3q25 .1-3q25 .2 . Further investigation by
FISH analysis with BAC clones confirmed the heterozygous deletion
at the same region . The genes COMMD2, RNF13, PFN2, SERP1,
EIF2A, SELT, SIAH2, CLRN1, and several open reading frames are included
in the deletion interval . Among them, some genes may be good
candidates for the congenital heart disease or other phenotypes .
P02.136
A patient with a 6p interstitial deletion and a complex
translocation involving chromosomes 2, 6, and 14
D. Misceo 1,2 , K. Bjørgo 1 , E. Ormerod 1 , Ø. Ringen 3 , C. van der Hagen 1 , M. Rocchi
2 , E. Frengen 1 ;
1 Department of Medical Genetics, Ullevål University Hospital and Faculty of
Medicine, University of Oslo, Oslo, Norway, 2 Department of Genetics and Microbiology,
University of Bari, Bari, Italy, 3 Eye Department, Ullevål University
Hospital, Oslo, Norway.
We describe a 5 years old patient with global developmental delay .
He lags about one year behind his peers . The language development
is most delayed, especially the pronunciation . As a baby he was quiet
and slept excessively . The patient has hypermetropia of 2 .5 diopters
bilaterally and minor exophoria . Eye examination revealed a chorioretinal
coloboma inferonasally in the left eye . He shows dysmorphic features:
hypertelorism, deep set eyes, prominent filtrum, slightly prominent
forehead, low set and backward rotated ears .
A combined approach of G banding, aCGH and FISH revealed complex
chromosome rearrangements, involving chromosomes 2, 6 and
14 . These rearrangements are de novo, since both parents have a
normal karyotype . He also has two healthy sibs .
Beside the reciprocal translocation between chromosome 2q and 6p,
we also detected an insertion of a large segment from chromosome 14
into chromosome 6p, and an extensively reshuffled 6p: chromosome
der(6)(p) also carries a 4 Mb interstitial deletion and a small paracentric
inversion .
Because of the high number of chromosome breakpoints in this patient
we cannot connect the involvement of each breakpoint to the clinical
phenotype. However, the most significant aberration is the 6p interstitial
deletion . Interstitial deletions of 6p are rare events that to our
knowledge previously have been reported in a total of eight patients .
We compare the clinical traits of our patient to the few cases of 6p
interstitial deletions previously described and we discuss the potential
role of TFAF2A and FOXC1 in relation to the choroidal coloboma .
P02.137
Dicentric inv Dup of the Whole 4p Without Deletion. Description
of the First case
L. Rodríguez 1 , M. Martínez-Fernández 1,2 , M. Aceña 1 , S. López Mendoza 3 ,
L. Martín Fumero 3 , M. Rodríguez de Alba 4,5 , M. Fernández 4,5 , M. Martínez-
Frías 1,4,6 ;
1 Est. Colaborativo Español de Malformaciones Congénitas del Centro de Investigación
sobre Anomalías, Madrid, Spain, 2 Centro de Investigación Biomédica
en Red de Enfermedades Raras (CIBERER), ISCIII,, Madrid,, Spain, 3 Servicio
de Pediatría. Hospital Nuestra Señora de la Candelaria,, Santa Cruz de Tenerife.
Islas Canarias., Spain, 4 Centro de Investigación Biomédica en Red de Enfermedades
Raras (CIBERER), ISCIII,, Madrid, Spain, 5 Servicio de Genética.
Fundación Jiménez Díaz., Madrid., Spain, 6 Departamento de Farmacología,
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