2009 Vienna - European Society of Human Genetics

Cytogenetics
P03.183
An atypical 7q11.23 deletion in a normal iQ Williams-Beuren
syndrome patient
E. Biamino 1 , C. Howald 2 , L. Micale 3 , B. Augello 3 , C. Fusco 3,4 , M. G. Turturo 3 , S.
Forzano 1 , M. Silengo 1 , G. B. Ferrero 1 , A. Reymond 2 , G. Merla 3 ;
1 Department of Pediatrics, University of Torino, Torino, Italy, 2 Center for Integrative
Genomics, University of Lausanne, Lausanne, Switzerland, 3 Medical
Genetics Unit, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo,
Italy, 4 PhD Program, Department of Biomedical Sciences, University of Foggia,
Foggia, Italy.
Williams Beuren syndrome (WBS, OMIM#194050) is a multisystemic
neurodevelopmental disorder caused by a hemizygous deletion of
1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency
of the ELN gene was shown to be responsible for supravalvular
aortic stenosis and generalized arteriopathy, while LIMK1, CYLN2 and
GTF2IRD1 genes were suggested to be linked to the specific cognitive
profile and craniofacial features. These insights for genotype-phenotype
correlations came from the molecular and clinical analysis of
patients with atypical deletions and mice models.
We report the detailed clinical and cognitive examinations together
with cytogenetics (FISH) and molecular (QPCR) analysis of a WBS
patient showing mild WBS physical phenotype and normal IQ. He
carries a shorter 1 Mb atypical deletion, which does not include the
GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our
results are consistent with the previous hypothesis that hemizygosity
of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms
and in the specific motor and cognitive deficits observed
in WBS patients.
P03.184
the elastin gene is not disrupted in a patient with a balanced
tarnslocation t(5 ;7)(q32;q11.23) and incomplete Williams-Beuren
phenotype
M. Chaabouni 1 , F. Abdelhedi 2 , I. Ouertani 1 , M. A. Ksentini 1 , R. Meddeb 1 , L. Ben
Jemaa 1 , H. Chaabouni 1 ;
1 Department of hereditary and congenital diseases, Charles Nicolle hospital,
tunis, Tunisia, 2 Department of hereditary and congenital diseases, Hedi Chaker
Hospital, sfax, Tunisia.
The Williams-Beuren syndrome is a complex developmental disorder
with multisystemic manifestations including supravalvular aortic stenosis
(SVAS), a typical face and a specific cognitive phenotype. Elastin is
one of the deleted genes in this contigous syndrome whose haploinsufficiency
causes cardiovascular malformations. Correlations between
deleted genes and observed phenotypes are not well established.
Here, we report the case of a 5 years and 6 months old boy referred to
us for psychomotor delay and mental retardation.
Physical examination showed a dysmorphic face with a broad forehead,
full cheeks, epicanthus,depressed nasal bridge, open mouth,
protruding lower lip. He also has a severe myopia. A mild mental retardation
was noticed, as our patient is attending school but having
attention difficulties.
Neither cardiovascular malformation nor abdominorenal anomalies
were found by ultrasound examination. However, karyotype showed a
reciprocal translocation between chromosomes 5 and 7: 46,XY,t(5;7)(
q32;q11.23). After FISH experiments with Vysis ELN probe and Vysis
EGR1 probe, we concluded that the breakpoint on chromosome 7 was
proximal to ELN and on chromosome 5 distal to EGR1. Further FISH
studies showed that the breakpoint on chromosome 7 is proximal to
the BAC RP11-313P13 (i.e 1Mb from ELN). We are studying the exact
breakpoint to determine the disrupted region which could help us to
better correlate features in Williams syndrome with candidate genes.
P03.185
Azoospermia due to a de novo balanced reciprocal translocation
(Y;3)(q12;q22)
F. Farzanfar, C. Azimi;
Department of Genetics, Cancer Institute, Imam Khomeini Hospital Complex,
Tehran, Islamic Republic of Iran.
It has been suggested that among infertile couples 4.5% of males and
6% of women have some sort of chromosomal aberrations. Aside from
sex chromosome abnormalities (males, 2% and females, 4.5%), balanced
reciprocal translocations are the most frequent chromosomal
aberrations with the frequency of about 1% for males and 0.7 for fe-
males. Although all of the chromosomes can be involved in reciprocal
translocations, chromosomes 12, 22 and Y are involved more often
than expected on the basis of their relative lengths. A balanced reciprocal
translocation between chromosome Y and autosomes has
been demostrated. The association between translocation (Y;1) and
azoospermia also has been suggested.
We report a balanced reciprocal (Y;3) translocation associated with
azoospermia which we could not find similar published case in the
literature. A 30-year-old man was referred to our department due to
infertility. Physical examination of patient was unremarkable. Testicular
sonography revealed a homogenous echo, and mild bilateral varicoceles.
The size of the right testis was 47x25 mm, and the left was
47x28 mm. His semen analysis showed: volume ( 0.8 ml ), count (
0.05 mill/ml ), motility ( 100% non-motile ). The levels of his folliclestimulating
hormone, luteinizing hormone, prolactin and testosterone
were within normal limits. Chromosomal study on his peripheral blood
was performed, using standard G-banding techniques, and revealed
that all his cells have a balanced translocation between chromosomes
number 3 and Y with a 46,X t(Y;3)(q12;q22) karyotype.
P03.186
AZF microdeletions in iranian non-obstructive azoospermia
patients
R. Mirfakhraie 1,2 , F. Mirzajani 1 , N. Salsabili 3 , M. Montazeri 1 , S. Kalantar 4 , M.
Houshmand 1 ;
1 National Institute for Genetic Engineering & Biotechnology, Tehran, Islamic Republic
of Iran, 2 Islamic Azad University of Tehran, Science & Research Branch,
Tehran, Islamic Republic of Iran, 3 Mirza koochak khan Hospital, Tehran University
of Medical Sciences, Tehran, Islamic Republic of Iran, 4 Clinical & Research
Center for Infertility, Yazd, Islamic Republic of Iran.
Genetic factors cause about 10% of male infertility. In the present study
the existence and or absence of 8 sequence tagged sites markers
representing AZF regions (AZFa, AZFb, AZFc and AZFd) was studied
using Multiplex PCR. Of the total 106 azoospermic men analyzed, 14
individuals (13.21%) showed Y chromosome deletion, of which deletion
in AZFb region was the most common (71.43%) followed by AZFc
(50%) , AZFd (42.86%) and AZFa (21.43%). None of these microdeletions
was detected in the control fertile group. Also in the case of AZFc
partial deletions, no significant statistical correlation was observed
between the incidences of gr/gr, b1/b3 and b2/b3 deletions and male
infertility (P values were 0.153, 0.465, and 0.447 respectively).
P03.187
molecular and cytogenetic analysis of Y chromosome
abnormalities in males with reproductive disorders
V. Cejnova 1 , P. Stolba 2 , V. Harmas 1 , M. Wilimska 1 , J. Lastuvkova 1 ;
1 Regional Health Corporation, Masaryk Hospital in Usti nad Labem, Department
of Medical Genetics, Usti nad Labem, Czech Republic, 2 Regional Health
Corporation, Masaryk Hospital in Usti nad Labem, Department of Transfusiology,
Usti nad Labem, Czech Republic.
Introduction: Approximately 10-15% of couples are affected by infertility.
The male factor of infertility (the azoospermia factor, AZF) was
mapped to three different subregions (AZFa, AZFb, AZFc) in Yq11
which are associated with spermatogenic failure. The aim of this study
was: 1) to determine the prevalence and type of microdeletions of the
Y chromosome of Czech males with reproductive disorders; 2) to describe
cytogenetic abnormalities.
Methods: Karyotypes and AZF microdeletions were analyzed in 136
males from patients with azoospermia and oligospermia. Genomic
DNA was extracted from peripheral blood samples and two multiplex
polymerase chain reactions (PCR) were performed using sequence
tagged sites (STSs) primers to confirm the presence or absence of Y
chromosome microdeletions (Simoni et al., 1999).
Results: Microdeletions of Y chromosome were detected in ten (7.35%)
patients. Among these, one had deletions in AZFa, three in AZFc,
three in AZFb+c and two in AZFa+b+c regions. In one case, the partial
deletion in AZFb (sY134) region was found. We present a molecular
and cytogenetic analysis of a mosaic 45,X/46,X,idic(Y) in patient with
isodicentric Y chromosome with two short arms and small portion of
the long arm (microdeletions in Yq11).
Conclusion: Screening for microdeletions in AZFa, b and c region of
Y chromosome showed a big variation among different studies. Our
study did not find any population dependent differencies in the preva-