2008 Barcelona - European Society of Human Genetics

Cytogenetics
Rennes, France, 4 Département de Génétique, INSERM U676, Hôpital Robert
Debré, AP-HP, Paris, France, 5 Département d’Histologie Embryologie Cytogénétique,
Hôpital Jean Verdier, Bondy, AP-HP, UFR-USMBH, Paris XIII, Paris,
France, 6 Service de Génétique Médicale, Rennes, France.
Background: Genome-wide screening of patients with mental retardation
using Array Comparative Genomic Hybridization (array-CGH) has
identified several novel imbalances. With this genotype-first approach,
the 2q22 .3q23 .3 deletion was recently described as a novel microdeletion
syndrome . We report two unrelated patients with a de novo
interstitial deletion mapping in this genomic region and presenting
similar “pseudo-Angelman” phenotypes, including severe psychomotor
retardation, speech impairment, epilepsy, microcephaly, ataxia and
behavioural disabilities .
Methods: The microdeletions were identified by array-CGH using oligonucleotide
and BAC-arrays, and further confirmed by Fluorescence
In Situ Hybridization (FISH) and semi-quantitative PCR .
Results: The boundaries and sizes of the deletions in the two patients
were different but an overlapping region of about 250 kb was defined,
which mapped to 2q23 .1 and included two genes: MBD5 and EPC2 .
The SIP1 gene associated with the Mowat Wilson syndrome was not
included in the deleted genomic region .
Discussion: Haploinsufficiency of one of the deleted genes (MBD5 or
EPC2) could be responsible for the common clinical features observed
in the 2q23 .1 microdeletion syndrome and this hypothesis needs further
investigation .
P02.165
Etiological investigation of the midline Facial Defects with
Hipertelorism by molecular and cytogenetic techniques
E. L. Freitas1 , S. M. Gribble2 , M. Simioni1 , E. Prigmore2 , N. P. Carter2 , V. L.
Gil-da-Silva-Lopes1 ;
1 2 Universidade Estadual de Campinas, Campinas, Brazil, The Wellcome Trust
Sanger Institute, Hinxton, Cambridge, United Kingdom.
The Midline Facial Defects with Hipertelorism (MFDH) are a heterogeneous
and rare group of craniofacial disorders mainly characterized
by ocular hypertelorism and bifid nose. The pathogenesis of these
conditions is still unknown . All 14 individuals in this study were previously
investigated by clinical, dysmorphologic and neurological evaluation,
skull and facial X-rays, computerized tomography and MRI of
the brain, and ophthalmologic and otorhynolaringologic evaluation and
GTG banding . The evaluations demonstrate facial alterations, structural
and functional anomalies of the central nervous system, indicating,
mainly, cortical migrations errors, perfusion variances and cerebella
involvement . Based upon these observations, we determined an initial
molecular investigation strategy . The phenotypes and a review of the
literature suggested genes related to face and CNS development such
as SHH, PAX3 and FGF8 may be involved in these disorders . These
genes have been reported to participate in embryological development
and are associated with some syndromes with craniofacial anomalies .
The SHH, PAX3 and FGF8 genes were screened by direct sequencing
and however mutations were found . To complement these studies, the
whole genome tiling path array-CGH technique was performed and
one deletion was found that affected PAX3 in a familial case .Other
copy number changes were detected and these findings are currently
being confirmed by FISH and PCR . These preliminary results suggest
our initial hypothesis that developmental genes, such as PAX3, play a
role in the MFDH etiology .
P02.166
Diagnosis of Miller-Dieker syndrome (MDS) by fluorescence in
situ hybridization (FisH)
M. Bassecourt, M. Alcaine, S. Izquierdo, E. Garcia, M. Calvo;
Hospital Universitario Miguel Servet, Zaragoza, Spain.
Introduction: Mieller Dieker Syndrome (MDS) involves a deletion of the
chromosomic band 17p13 .3 which contains the gene called LIS 1 (lissencephaly-1)
. It is a syndrome with a very low frecuency, estimated
in 11,7 cases for each million of births, although the incidence and the
prevalence are probably higher .
Objective: The aim of this study is to report a case from “breast-fed
baby” with a extensive record: premature baby, dismorfic phenotype,
lissencephaly, agenesis of the corpus callosum and septum pellucidum.
Molecular techniques are used to confirm the submicroscopic
deletion on 17p13 .3 .
Methods: It was realized a double culture of lymphocytes with conventional
banding GTG high resolution, followed by a FISH with the probe
LSI 1 (maps to the 17p13 .3 region on chromosome 17 containing the
gene localization of the MDS) .
Results: The fetu´s karyotype is: Male: 46, XY, del (17) (p13 .3) . After
hybridization with the probe, the SpectrumOrange LSI 1 signal was
present in only one chromosome 17 and the SprectrumGreen LSI
RARA 17q21 .1 signal (control) was present in both chromosomes 17 .
Male: 46, XY . ish del (17)(p13 .3 p13 .3)(LIS1-) .
The parents´ karyotypes are in progress .
Conclusions: Our results postulate that approximately 90 percent of
the patients with MDS phenotype show deletion of the band 17p13 .3
but only in a 50 percent of these cases the deletion is visible by
high resolution cytogenetic techniques. The own specificity of FISH
achieves cytogenetic diagnosis that rarely it is obtained with banding
techniques, unless prometaphasic chromosomes with high number of
bands would be used .
P02.167
the results of missed abortus testing from istanbul memorial
Hospital
O. Oner, G. Ozgon, C. Aslan, B. Onal, F. Fiorentino;
Genoma Turkey, istanbul, Turkey.
INTRODUCTION: The aim of this study is the retrospective data collection
for patients underwent IVF treatment and spontaneous pregnancy
lost between 2000-2007 for missed abortus with indications
such as; advanced maternal age (ama), recurrent implantation failure
(rif), recurrent pregnancy lost (rpl) and male factor .
MAT- METHOD: Tissue cultures were performed for missed abortus
materials . Culture developments were observed and underwent harvesting
steps in the optimum timing . Slides were stained with giemsa
staining techniques (GTG) and 30 cells were counted .
Between years 2000-2007, tissue cultures were performed to 308
patients in our center . 149 of them were IVF patients, and 159 were
spontaneous missed abort .
38/149 IVF and 48/159 spontaneous missed abort cases had abnormal
karyotypes . We also analiysed Trisomy 9, Trisomy 8, Trisomy 4
and Mosaic X in 4 PGD cases .The indications and chromosome analysis
results of 38/149 IVF cases are represented in the table .1 below .
Table 1
Indications Results
RPL
(n=3)
AMA
(n=4)
RIF
(n=22)
Male
Factor(n=9)
Trisomy 8 (n=1)
Triploidy (n=1)
Trisomy X/ Trisomy 20 (n=1)
Trisomy 13 (n=1)
Trisomy 16 (n=1)
Trisomy 18 (n=1)
Trisomy 13/16 (n=1)
Trisomy 3 (n=1) Trisomy 13/16 (n=1)
Trisomy 12 (n=2) Trisomy 16/20 (n=1)
Trisomy 13 (n=1) 45,X (n=1)
Trisomy 15 (n=1) 47,XXY (n=1)
Trisomy 16 (n=4) Tetraploidy (n=3)
Trisomy 18 (n=1) del(1)(q32 .1q42 .1) (n=1)
Trisomy 19 (n=1) der(14;14),+14 (n=1)
Trisomy 20 (n=1)
Trisomy 22 (n=1)
45,X (n=4) Trisomy 16 (n=1)
Trisomy 4 (n=1) inv(10q) (n=1)
Trisomy 7 (n=1)
Trisomy 9 (n=1)
Spontaneous missed abortus results
(n=48)
Trisomy 3 (n=1) Trisomy 21 (n=3)
Trisomy 6 (n=2) Trisomy 22 (n=6)
Trisomy 7 (n=1) Triploidy (n=5)
Trisomy 8 (n=3) Tetraploidy (n=1)
Trisomy 16 (n=5) 45,X (n=11)
Trisomy 15 (n=5) Mosaic X (n=1)
Trisomy 17 (n=1)
Trisomy 18 (n=1)
Trisomy 20 (n=2)