2009 Vienna - European Society of Human Genetics

Cytogenetics
use of metaphase analysis with conventional Giemsa-staining, present
study investigated both the groups. After signing a consent form,
volunteers provided blood samples (5 ml) to establish cell cultures at
72 h. For karyotyping, minimum 40 complete metaphase cells from
each subject was evaluated. Higher degree of chromosomal - type and
chromatid type aberrations were observed in experimentals compared
to controls. Present study shown that the arsenic caused an increase
in CA. The mean frequencies per 100 metaphase of major CA type
(chromosome rings, translocations, and dicentrics) of the workers and
the non-exposed controls were 0.91 and 0.24 respectively. Gene-gene
and gene-environment interactions are involved in arsenic-induced
health hazards through toxicological mechanisms including genomic
instability and oxidative stress.
P03.010
cytogenetic analysis in BOH cases- an indian experience
R. Talwar-Sethi, S. K. S. Vats, M. K. Verma;
Super Religare Laboratories (SRL), Gurgaon, India.
Chromosomal imbalance has been identified as a major cause for
spontaneous pregnancy loss, infertility and childhood disability thereby,
contributing significantly to the genetic burden on society. The diagnosis
of such chromosomal anomalies in cases with bad obstetric history
(BOH) can be made by conventional cytogenetics which involves
karyotyping of GTG banded chromosome preparations obtained from
whole blood. In the present study, conventional cytogenetic analysis
was used to analyze peripheral blood samples from 167 individuals
with BOH. Of these 167 cases, 145 presented with a history of spontaneous
abortions (mean of 2 abortions) that were mainly in the first trimester.
The remaining 22 cases included 20 with a history of children
with congenital anomalies and 2 with death of children due to unknown
causes. Cytogenetic analysis revealed chromosomal abnormalities in
10 cases. Robertsonian translocation between chromosomes 13 and
14 was reported in one case. Two cases revealed pericentric inversions
in chromosomes 3 and 9 respectively. Novel cytogenetic anomalies
like t(9;20) and t(1;13) were also observed in two cases. Three
cases revealed heteromorphic variants in chromosome 1 (n=1) and 9
(n=2). Another case revealed addition of genetic material in the short
arm of chromosome 15 that has not yet been reported in literature,
to the best of our knowledge. The detection of these chromosomal
anomalies, few of which are novel, in cases with BOH reiterates that
cytogenetic analysis is a ‘gold standard’ for screening cases with BOH
where structural anomalies are observed more frequently than aneuploidies.
P03.011
Identification of copy number variants associated with BPES-like
phenotypes
A. C. J. Gijsbers 1 , B. D’haene 2 , Y. Hilhorst-Hofstee 1 , M. Mannens 3 , B. Albrecht
4 , J. Seidel 5 , D. R. Witt 6 , M. K. Maisenbacher 7 , B. Loeys 2 , T. van Essen 8 , E.
Bakker 1 , R. Hennekam 9 , M. H. Breuning 1 , E. De Baere 2 , C. A. L. Ruivenkamp 1 ;
1 Center for Human and Clinical Genetics; Leiden University Medical Center
(LUMC), Leiden, The Netherlands, 2 Center for Medical Genetics, Ghent University
Hospital, Ghent, Belgium, 3 Center for Clinical Genetics, Amsterdam
Medical Center, Amsterdam, The Netherlands, 4 Institut fur Humangenetik,
Universtaetsklinikum Essen, Essen, Germany, 5 Department of Pediatrics, SRH,
Klinikum Gera, Gera, Germany, 6 Genetics Department, Kaiser Permanente,
San Jose, CA, United States, 7 Devision of Genetics, Department of Pediatrics,
University of Florida, Gainesville, FL, United States, 8 Department of Genetics,
University Medical Center Groningen, Groningen, The Netherlands, 9 Department
of Pediatrics, Amsterdam Medical Center, Amsterdam, The Netherlands.
Blepharophimosis-Ptosis-Epicanthus inversus Syndrome (BPES) is a
well characterized rare syndrome that includes an eyelid malformation
associated with (type I) or without premature ovarian failure (type II).
Patients with typical BPES have four major characteristics: blepharophimosis,
ptosis, epicanthus inversus and telecanthus. Mutations in
the FOXL2 gene, encoding a forkhead transcription factor, are responsible
for the majority of both types of BPES. However, many patients
with BPES-like features, i.e. having at least 2 major characteristics
of BPES, have an unidentified cause. Here, we report on a group of
27 patients with BPES-like features, but without an identified genetic
defect in the FOXL2 gene or flanking region. These patients were analyzed
with whole-genome high-density arrays in order to identify copy
number variants (CNVs) that might explain the BPES-like phenotype.
In 9 out of 27 patients (33%) CNVs not previously described as polymorphisms
were detected. Four of these patients displayed psychomotor
retardation as an additional clinical characteristic. In conclusion,
we demonstrate that BPES-like phenotypes are frequently caused
by CNVs, and we emphasize the importance of whole-genome copy
number screening to identify the underlying genetic causes of these
phenotypes.
P03.012
mapping of candidate Regions and Genes for congenital
Anomalies of the Kidneys and Urinary tract (cAKUt) using
Array-Based comparative Genomic Hybridization
C. Landwehr 1 , S. Weber 2 , M. Renkert 2 , A. Hoischen 1 , E. Wühl 2 , B. Radlwimmer
3 , F. Schäfer 2 , R. G. Weber 1 ;
1 Institute of Human Genetics, Rheinische Friedrich-Wilhelms-University, Bonn,
Bonn, Germany, 2 Division of Pediatric Nephrology, University Children’s Hospital,
University of Heidelberg, Heidelberg, Germany, 3 Department of Molecular
Genetics, German Cancer Research Center, Heidelberg, Heidelberg, Germany.
Congenital anomalies of the kidneys and urinary tract (CAKUT) are
frequently associated with malformations of other organs. The etiology
of maldevelopment often remains unknown. Therefore, we wanted to
identify novel genomic regions associated with the CAKUT phenotype.
We analyzed 30 unexplained CAKUT-patients with at least one additional
extrarenal symptom using genome-wide array-CGH. In 3 patients,
causal imbalances were detected. Patient HD1 was affected
by the CAKUT-phenotype of hypospadias in addition to extrarenal
anomalies. In the patient and his brother with a similar phenotype, array-CGH
detected a terminal loss of 0.59Mb in chromosomal band
1q44 and a terminal gain of 6.55Mb in 16q23.3-q24.3 due to an unbalanced
1;16-translocation according to FISH-analysis. A balanced
1;16-translocation was detected in both patients’ unaffected father. In
patient HD16 presenting with renal hypoplasia and proximal ureteral
stenosis in addition to mental retardation, macrocephaly, atresia of the
auditory canal, and microtia, array-CGH detected a gain of 2.4Mb in
1q21.1. In the patient’s unaffected father, a gain of 1.3Mb in 1q21.1q21.2
was found involving the distal part of the patient’s gain, for which
benign copy number variation was described. In patient HD24 affected
by renal dysplasia with hydronephrosis and extrarenal abnormalities,
array-CGH identified a loss of 11.93Mb in 3q23-q25.1, confirmed and
shown to be de novo by FISH-analysis. In summary, our study provides
evidence that 1q44-loss and/or 16q23.3-q24.3-gain may be associated
with hypospadias development, a uniallelic deletion in 3q23-q25.1 can
cause renal dysplasia and hydronephrosis and that a renal phenotype
may be associated with the 1q21.1-duplication genomic disorder.
P03.013
cytogenetic study of tannery industry workers exposed to
chromium compounds
M. Arun, V. Balachandar, A. Karthick kumar, P. Manikantan, S. Mohanadevi, K.
Sasikala;
Bharathiar University, Coimbatore, India.
Chromium (Cr) is a metallic element which is listed by the Environmental
Protection Agency as one of 129 priority pollutants. Chromium
is considered one of the 14 most noxious heavy metals. Of the 1,083
tanneries in India, more than half, i.e. 577 are in Tamilnadu and of the
577, Chennai City and the North Arcot district account for as many as
397 tanneries. The production in Tamil Nadu is 44% of the total all-
India production. Hence, the present investigation has been carried
out the 4 regions in Tamilnadu namely Vanniyampadi; Rani pet; Ambur
and Erode. The objective of this study is to investigate the relationship
between Cr workers and chromosomal alteration in the above
population. In the present study totally 82 samples including 41 experimentals
and 41 controls were selected. After signing a consent form,
volunteers provided blood samples (5 ml) to establish cell cultures at
72 h. For karyotyping, 40 complete metaphase cells from each subject
were evaluated. Higher degree of chromosomal and chromatid type
aberrations were observed in experimentals compared to controls.
Statistically significant results were obtained with the value (P