2009 Vienna - European Society of Human Genetics

Cytogenetics
P03.057
Pathological cytogenetic findings of chromosome 21 prenatally
diagnosed in medical Genetic center of Novi sad
J. D. Jovanovic Privrodski, I. Kavecan, M. Kolarski, A. Krstic, L. Gacina, V.
Cihi, J. Rudez, T. Tarasenko, M. Fojkar, D. Radovanov;
Institute for Children and Youth Health Care Vojvodina, Novi Sad, Serbia.
We present results of prenatally detected trisomy of chromosome 21 in
Medical Genetic Centre in Novi Sad which is a part of Institute for Children
and Youth Health Care of Vojvodina. Prenatal genetic screening
of fetal abnormalities is performed using detailed analyses of pedigree,
maternal and paternal age, biochemical screening and expert ultrasound
results such as thickness of nuchal translucency, absent nasal
bone, hyperechogenic bowel, short femur, and other.
In this paper we present incidence of prenatally detected trisomies of
chromosome 21 during last eight years (2000-2008) in Medical Genetic
Centre in Novi Sad, Vojvodina northern part of Serbia with around
2.000.000 inhabitans. During last eight years we detected 113 trisomy
of chromosome 21 (105 classical trisomies, 5 mosaical forms, 3 translocational
forms), that is 38.96% of all prenatally detected chromosomal
anomalies (N= 113/290; 38.96%).
P03.058
Dicentric Y chromosome in turner syndrome
D. Jardan, V. Radoi, D. Mierla;
Life Memorial Hospital, Bucharest, Romania, Bucharest, Romania.
Present case relates to a 19 years old girl with Turner syndrome phenotype
referred to our clinic for cytogenetic analysis. Patient presented
primary amenorrhea and no signs of virilisation. Cytogenetic analysis
revealed mosaic karyotype 46,X, dic (Y)(q11.2),45,X. FISH analysis
confirmed presence of a dicentric Y chromosome. FISH analysis was
performed using centromeric probe for X chromosome and specific
probe for SRY region of Y chromosome.
Presence of Y chromosome material is associated with a ~12% risk
of gonadoblastoma. Gonadoblastomas may transform into malignant
germ cell neoplasm.
Conclusions: testing for Y chromosome material in Turner syndrome
should be performed in any Turner syndrome patient.
P03.059
Parental Origin of X-chromosome in turner syndrome patients.
I. M. R. Hussein1 , A. Kamel1 , H. H. Afifi1 , A. Cicognani2 , L. Mazzanti2 , L.
Baldazzi2 , A. Nicoletti2 , H. F. Kayed1 , W. Mahmoud1 , A. Amer3 ;
1 2 National Research Center, Giza, Egypt, University of Bologna, Bologna, Italy,
3Cairo University, Cairo, Egypt.
Turner syndrome (TS) is a chromosomal disorder in which all or part
of one X chromosome is missing.Objectives: To detect the spectrum
of chromosomal abnormalities;to determine the parental origin of the
abnormality,and correlate it with the patient phenotype. The study included
42 females who had Turner stigmata(30 Egyptian;12Italian).
The patients were classified into: Group (A) patients with only 45,X
karyotype (n=16), group (B)patients having either mosaic cell lines or
other X-chromosome abnormalities(n=26). Numerical X-chromosome
mosaicism was observed in 22 patients(52%),7 patients (17%) had an
isochromosome X,3 patients (7%) had a ring X chromosome,1 patient
(2%) had a deletion of the short arm of the X chromosome, 3 patients
(7%) had an isochromosome X and 1 patient (2%) had a deletion of the
long arm of the X chromosome.FISH technique was performed using
Alpha satellite DNA cocktail probe for chromosome X and Y. A second
cell line was detected in 4 patients who were diagnosed as having
45,X. We used PCR-based typing of highly polymorphic microsatellite
markers distributed along the X chromosome to detect origin of the X
chromosome. Parental origin of the single X chromosome was maternal
in 67% of these patients, while in group (B), parental origin of the
normal X chromosome was maternal in 11 patients (65%), paternal in
6(33%), uninformative in 1 patient (6%). No evidence for X-imprinting
of the studied physical features in TS was observed. Thus, there is no
apparent clinical indication for investigation of X-chromosome parental
origin in individuals with TS.
P03.060
XX male patient with Robertsonian translocation der(13;14)
T. G. Tsvetkova, V. B. Chernykh, V. A. Galkina, L. V. Shileiko, L. F. Kurilo, N. V.
Kosyakova, O. P. Ryzhkova, A. V. Polyakov;
Research Centre for Medical Genetics, Russian Academy of Medical Sciences,
Moscow, Russian Federation.
Introduction: Commonly XX sex reversal is a result from translocation
of Yp material including SRY gene onto the X chromosome.
Materials and Methods: We report a 27-year-old XX male with Robertsonian
translocation. The proband was born to a 29-years woman
from a second pregnancy. The first pregnancy has ended with childbirth
of the healthy girl. The proband’s sister is healthy, married, has
the healthy daughter. The patient was referred to our centre with a 3
year history of male factor infertility. The proband had fully mature male
genitalia with descended in the scrotum hypoplastic testes and no sign
of undervirilization. His weight was 59 kg, height - 166 cm. Intelligence
was normal. Semen analysis showed severe oligoasthenoteratozoospermia
(sperm count 0.1 mln/ml).
Chromosome analysis was performed on cultured PHA-stimulated peripheral
blood lymphocytes with GTG-, C- and QFH-staining in accordance
with standard techniques. DNA was extracted from peripheral
leukocytes by a standard method. Molecular analysis of Y chromosome
loci was performed using multiplex PCR amplifications for SRY,
AMELX/AMELY, ZFY/ZFX, and seven Yq-specific STSs: sY84, sY86,
sY615, sY127, sY134, sY254 and sY255.
Results: Cytogenetic examination showed 45,XX,der(13;14)(q10;q10)
karyotype in all of 50 analyzed metaphases. PCR amplifications were
positive for SRY, AMELX, AMELY, ZFX, ZFY and negative for all analyzed
Yq11 loci. The origin of Robertsonian translocation (de novo or
inherited) was not found because of a material from the proband’s parents
and sister was not available.
Conclusion: To our knowledge we reported the first XX sex reversed
patient associated with Robertsonian translocation.
P03.061
Wide spectrum of Peters and Axenfeld-Rieger anomalies
secundary to a 4q25 microdeletion encompassing the PITX
gene
M. Mathieu 1 , G. Morin 1 , B. Demeer 1 , J. Andrieux 2 , F. Imestouren-Goudjil 1 , M.
Vincent 3 , A. Receveur 4 , H. Copin 4 , B. Devauchelle 5 ;
1 Unité de Génétique Clinique - CHU d’Amiens, Amiens, France, 2 Hôpital Jeanne
de Flandre - CHRU de Lille, Lille, France, 3 Hôpital Purpan - CHU de Toulouse,
Toulouse, France, 4 Laboratoire de Cytogénétique - CHU d’Amiens, Amiens,
France, 5 Service de Chirurgie Maxillo-Faciale - CHU d’Amiens, Amiens, France.
Many genes are involved in the ocular development. The alterations
of some of them are responsible of the Peters or the Axenfeld-Rieger
anomalies (PITX2, FOXC1, PAX6 …). In theses conditions, angle
anomalies are responsible of glaucoma in 50% of cases, usually congenital
and difficult to manage. When they are associated with extraocular
symptoms, the name of Rieger or Peter + syndrome can be
used. In these entities, the mode of inheritance is usually autosomal
dominant.
We report a 21-year-old patient, third child of healthy non-consanguinous
parents with a negative familial history. He presented a Peters
anomaly of the right eye requiring an iridectomy at 3 months of age,
and an Axenfeld-Rieger anomaly of the left eye associated with a glaucoma
at the age of 10. During childhood, he beneficiated of several
surgical interventions that concerned umbilical hernia, Meckel diverticulum,
bifid uvula, posterior sub-mucous cleft palate, pharyngoplasty
and tympanoplasty. He developed dysmorphic features including flat
malar region and retrognathia requiring surgical repair at the age of
16. He also presented hypodontia and persistence of lacteal teeth.
He had a normal mental development, a normal puberty and a normal
stature (1m80), but secondary to his visual impairment, he studied in
a special school.
Genetic investigations were negative for the standard karyotype and
the sequencing of the genes PITX2, FOXC1 and PAX6. The array-
CGH exhibited a de novo 1.7 Mb deletion at the locus 4q25 encompassing
13 genes including PITX2.