2009 Vienna - European Society of Human Genetics

Cytogenetics
P03. cytogenetics
Recurrent spontaneous abortions due to a homologous
Robertsonian translocation (13q13q)
A. Faraj Pour, C. Azimi, M. Khaleghian;
Department of Genetics, Cancer Institute, Imam Khomeini Hospital Complex,
Tehran University of Medical Sciences, Islamic Republic of Iran.
Balanced Robertsonian translocations are relatively common in different
populations, occurring at a frequency of about 1 in 1100 livebirths.
The proportion of these translocations that involve homologous chromosomes
appears to be extremely small. Robertsonian translocation
between two chromosomes 13 is a rare event, and should not manifest
any obvious phenotypicl effects. Theoretically, carriers of homologous
Robertsonian translocations are unable to produce normal children
since all their gametes should be either disomic or nullisomic for the
chromosome involved in the translocation. Our case was a 31 year old
woman who presented with three spontaneous abortions (at 12, 9 and
8 weeks, respectively). Her hysterosalpingography was normal. Her
laboratory tests including FSH, LH, Progesterone, Prolactin, Toxoplasmosis,
Listeriosis and TORCH were normal. She had three brothers
and three sisters, all healthy and married, with a few normal children.
Chromosome analysis was performed on cultured cells according to
standard methods from the patient’s peripheral blood samples. All
analyzed mitoses had 45 chromosomes with a derivative chromosome
consisting of the long arms of the two chromosomes 13. The resulting
net imbalance was loss of the short arms of both chromosomes 13.
Her karyotype showed: 45,XX, der(13;13)(q10;q10). Cytogenetic studies
of her parents were normal.
P03.002
the 1q-syndrome: A case report and literature review
A. Zagorac, N. Marcun Varda, N. Kokalj Vokac;
University Medical Centre Maribor, 2000 Maribor, Slovenia.
Deletions of the long arm of chromosome 1 have been reported in
numerous patients, with breakpoints occurring along the entire length
of the q arm, causing clinical differences. Specific phenotypic findings,
resembling a distinct syndrome, are present in cases with terminal
deletions at 1q42 and 1q43. Monosomy 1q42-qter seems to be associated
with characteristic manifestations. On these basis, molecular
techniques are important in order to correctly define the deleted segment,
and establish accurate genotype - phenotype correlations.
We provide a clinical description of a girl with de novo terminal 1q43qter
deletion.
The proband has been recognized as an infant with intrauterine growth
retardation and generalized muscular hypotonia, microcephaly, epichanthal
folds, telechantus, enophtalmus, short eye openings with lateral
blepharophimosis, small, broad and flat nose, low-set ears, higharched
palate and short neck. Valgus deformity of feet was present
with short right Achilles tendon.
Magnetic resonance of the brain revealed agenesis of the corpus callosum,
ventriculomegaly and enophtalmus. She has seizures.
Cytogenetic analysis of peripheral blood showed a de novo terminal
chromosome 1 long arm deletion, confirmed with Subtelomeric FISH
(Multiprobe-T-System, CytoCell). To define the extent of the deletion
and the breakpoint location we performed 244k array-CGH (Agilent
Technologies, USA) demonstrated a loss of 9.4 Mb genomic material
and the breakpoint 1q43 (at 237.6 Mb).
The patient’s features are compared with those of other patients with
similar deletions, and variable phenotypic findings due to different deleted
chromosomal segments are discussed.
P03.003
Partial monosomy of distal 2q and partial trisomy of distal 2p
in an adult mentally retarded patient, derived from a paternal
inversion
S. Ghasemi Firouzabadi 1 , F. Mojahedi 2 , F. Behjati 1 , K. Kahrizi 1 , M. Ataei Kachoui
1 , H. Darvish 1 , G. Bahrami Monajemi 1 , H. Najmabadi 1 ;
1 Genetics Research Center, University of Social Welfare and Rehabilitation
Sciences, Tehran, Islamic Republic of Iran, 2 Mashhad Medical Genetics Counselling
Center, Mashhad, Islamic Republic of Iran.
We describe a 24 year old mentally retarded and dysmorphic Iranian
male patient with partial monosomy for distal 2q and partial trisomy for
distal 2p. The patient’s karyotype is 46,XY,rec(2)dup(2p)inv(2)(p25.1
q37.3)pat. Chromosome analysis in the father showed a pericentric
inversion of chromosome 2, described as 46,XY,inv(2)(p25.1q37.3).
The proband’s karyotype is a recombinant product of the paternal inversion.
Parents are consanguineous, with one normal daughter and the affected
son. Both father and grandmother are deaf. The patient has moderate
mental retardation with developmental delay. The clinical features
include prominent arachnodactyly in feet and slim lower limbs, speech
delay, poor coordination, prominent supraorbital ridge, contracture
deformity of PIP, hands ulnar deviation, mild genuvalgus, mild facies
asymmetry and retrognatia, thick and malformed auricles, refractive
errors (myopia and astigmatism), prominent nose, with lipoma on the
face and multiple large acnea and scars. Most of the recorded clinical
features include the reported features of partial trisomy of distal part of
the short arm of chromosome 2. However, additional clinical features
which are not characteristic of the observed chromosome imbalances
are present. Complementary work for further characterization of the
deleted and duplicated chromosome segments is underway.
P03.004
Nonmalignant aneuploidization in the human brain:
chromosome instability can mediate neurodegeneration in
Alzhemer’s disease and ataxia-telangiectasia
I. Y. Iourov 1,2 , S. G. Vorsanova 1,2 , T. Liehr 3 , A. D. Kolotii 2 , M. K. Tagirova 1 , Y. B.
Yurov 1,2 ;
1 National Research Center of Mental Health, RAMS, Moscow, Russian Federation,
2 Institute of Pediatrics and Children Surgery, Rosmedtechnologii, Moscow,
Russian Federation, 3 Institute of Human Genetics and Anthropology, Jena,
Germany.
Chromosome instability (CIN) manifesting as aneuploidy is usually associated
with tumorigenesis. However, recent studies have shown that
phenomena related to CIN (cell cycle errors, aneuploidy) are observed
in the diseased (nonmalignant) brain tissues. The latter phenomenon
was recently observed in neurodegenerative disorders. To test a possible
link between CIN and neurodegeneration, we have analyzed interphase
chromosomes in the Alzheimer’s disease (AD) and ataxia-telangiectasia
(AT) brain. By means of interphase chromosome-specific
multicolor banding (ICS-MCB) and interphase FISH, we monitored
chromosome complement in about 500,000 neural cells derived from
the cerebral cortex of AD, AT and normal human brain (control samples).
We have established the mean rate of stochastic aneuploidy
per “mean” human chromosome as 0.5% in controls (the normal human
brain, 95%CI 0.2-0.7%; SD 0.2%). The AT brain demonstrated a
dramatic 2-to-5 fold increase of stochastic aneuploidy randomly affecting
different chromosomes (mean 2.1%; 95%CI - 1.5-2.6%; SD 0.8%).
The overall proportion of aneuploid cells in the brain of AT individuals
was estimated at 20-50%. The level of stochastic aneuploidy in the AD
brain was slightly increased compared with controls. However, a dramatic
10-fold increase of cells with unstable chromosome complement
affected by chromosome 21 hypoploidy and hyperploidy was detected
in the AD brain (6-15% versus 0.8-1.8% in control). Thus, CIN manifested
as aneuploidy does present in the AD and AT brain. Our data
indicate that CIN mediated by neural aneuploidization does not lead to
tumorigenesis but potentially mediate neurodegeration in these devastative
brain diseases. Supported by Philip Morris USA.
P03.005
Evaluation of Amenorrhea: cytogenetic investigation in a
tunisian cohort
R. Bhouri 1,2 , O. Kilani 1 , W. Ayed 1 , H. Elloumi 1 , F. Talmoudi 1 , H. Guermani 1 ,
N. Abidli 1 , I. El Kamel - Lebbi 1 , S. Abdelhak 2 , N. Bouayed-Abdelmoula 3 , A.
Amouri 1,2 ;
1 Cytogenetic Laboratory, Pasteur Institute, Tunis, Tunisia, 2 Molecular Investigation
of Genetic Orphan Diseases Research Unit (MIGOD), UR26/04, Pasteur
Insitute of Tunis, Tunis, Tunisia, 3 Laboratoire d’Histologie Embryologie, Faculté
de Médecine de Sax, Sfax, Tunisia.
Chromosomal abnormalities described in primary and secondary
amenorrhea range from X chromosome abnormalities such as Turner
syndrome to assorted deletions and translocations to mutations in specific
genes.
Sixty five women were referred to our Cytogenetic laboratory for chromosomal
exploration because of primary or secondary amenorrhea.
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