European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cytogenetics
malities and feeding difficulties. Hypotonia and hyperextensible joints
can result in delayed attainment of motor milestones. Inv dup(15) syndrome
presents peculiar physical findings (muscle hypotonia, minor
facial dysmorphisms), mental retardation, seizure, autism.
An 11 years old boy with mild mental retardation showing some of these
anomalies was referred to our examination. He was born at term with
eutocic delivery with normal auxologic parameters. Phisycal examination:
talus valgus pronate feet, gastroesophageal reflux, hypotonia
and feeding difficulties. Later, he manifested systemic hypertension,
growth (weight/height < 3 rd centile) and psychomotor delay. Echocardiography
showed a mild supravalvular aortic stenosis, hypothyroidism
was excluded. Calcium blood profile was normal. Cytogenetic analysis
revealed this karyotype: 47,XY,+inv dup(15)(q12)de novo.
Although some features of the patient such as cortex anomalies, short
and stubby hands and feet were specific of the iso dic(15), the peculiar
facies and cardiac defect suggested a WBS.
Molecular cytogenetic analysis (FISH) was performed with WBSCRspecific
probe, the presence of specific microdeletion in 7q11.2 was
confirmed. In this work, we compare the phenotype of patient with both
syndromes to evaluate the different contribution of concomitant chromosomal
anomalies.
P0349. Clinical findings in pericentric inversion of chromosome
9 - three years experience
M. Volosciuc, E. Braha, M. Gramescu, C. Rusu, M. Covic;
University of Medicine and Pharmacy, Iasi, Romania.
Pericentric inversion of chromosome 9 is one of the most frequent
structural balanced chromosomal aberrations. Commonly it is considered
as a normal variant of karyotype.
We reported 6 cases analyses over a three years period. Age of diagnosis
was under 18 years (2 cases) and over 18 years (4 cases).
The motivation for genetic consultation was repeated miscarriage (3
cases), multiple malformations in a new-born who died in the neonatal
period (1 case) and mental retardation, dysmorphic face (2 cases).
The karyotype showed pericentric inversion of chromosome 9 in all
cases. In a single case we detected a complex anomaly - 45,X,inv(9)/
46,XX,inv(9) - Turner syndrome.
It is difficult to assess the correlation between clinical signs and pericentric
inversion of chromosome 9. Genetic counselling and prenatal
diagnosis is helpful for most families.
P0350. Breakpoint cloning and haplotype analysis of a
novel cytogenetic variant consisting of a 12 Mb inversion on
chromosome 10, inv(10)(q11.22;q21.1)
M. Entesarian1 , B. Carlsson1 , E. Stattin2 , E. Holmberg3 , I. Golovleva2 , M. R.
Mansouri1 , N. Dahl1 ;
1 2 Uppsala University, Uppsala, Sweden, Umea University Hospital, Umea, Sweden,
3Sahlgrenska University Hospital/East, Gothenburg, Sweden.
We have identified an inherited paracentric inversion of chromosome 1
0[inv(10)(q11.22;q21.1)] revealed by high resolution karyotyping. A detailed
mapping of the inversion was done through fluorescence in situ
hybridization (FISH) and Southern blot hybridization in three non-related
Swedish individuals. Cloning and sequencing of the breakpoints
revealed that the inversion was identical in the three individuals. The
inversion spans 12 Mb and it is almost perfectly balanced at the nucleotide
level. No predicted transcripts or known genes are disrupted by
the inversion breakpoints. The 10q11.22 breakpoint is located within a
long terminal repeat (LTR) and the 10q21.1 breakpoint is 900 bp away
from a short interspersed nuclear element (SINE). Haplotype analysis
of the three individuals and their parents indicated that a shared haplotype
was inherited with the chromosome 10 inversion which favours
a single event for the inversion. A retrospective study of amniocenteses
and blood analyses performed in Sweden showed presence of the
inversion in 7 out of 8,896 amniocenteses and in 3 out of 2362 blood
analyses. In all cases the inversion was inherited from one of the parents.
From our results, we suggest that the inv(10)(q11.22;q21.1) is a
rare variant and that it is identical by descent.
P0351. Molecular and cytogenetic analysis in IVF failure cases
M. B. Shamsi 1 , R. Kumar 1 , R. Dada 1 , M. Tanwar 1 , G. Idris 1 , R. K. Sharma 2 , R.
Kumar 1 ;
1 AIIMS, New Delhi, India, 2 Army Research and Referral Hospital, New Delhi,
112
India.
Chromosomal abnormalities in infertile couples results in spermatogenic
arrest, premature ovarian failure, implantation failure and consequently
failure of InVitro fertilization (IVF). The aim of the study was to
determine genetic basis for recurrent ART/IVF failure. Thirty eight infertile
couples with IVF failure having poor blastocyst development and
implantation were analyzed cytogenetically and for molecular analysis
of AZF loci in the men. Two females with recurrent IVF failure showed
partial deletion of Xq and the other female had 10% cell line showing
deletion of pericenteromeric region of long arm of chromosome
number 1. Of these couples microdeletion analysis of 30 cytogenetically
normal infertile men, only two cases showed deletion; one with
AZFc loci and the other case had deletion of AZFb loci. The couples
where female partner had deletion of long arm of X chromosome(Xq-)
resulted in repeated failure of blastocyt development, in 4 IVF cycles.
The case with AZFb microdeletion had maturation arrest and case
with AZFc deletion had hypospermatogenesis. In these cases sperms
could be retrieved from the testis and to be used for IVF or Intracytoplasmic
sperm injection. (ICSI). In cases with sex chromosomal and
autosomal aberrations there is probability of poor embryo development
and consequently poor implantation, which may be a result of
high segregation abnormalities and may negatively affect the outcome
of assisted reproductive techniques. ART is a very expensive technique
and recurrent ART/IVF failure results in severe financial stress
coupled with emotional stress, thus all couples opting for ART must
undergo genetic analysis.
P0352. An unusual 11q deletion derived from a complex maternal
karyotype in a Jacobsen-like patient
L. J. C. M. van Zutven, Y. van Bever, C. van Nieuwland, D. van Opstal, L. J. A.
Corel, C. H. Wouters, P. J. Poddighe;
Erasmus MC, Rotterdam, The Netherlands.
We present a family with multiple cytogenetic abnormalities, identified
through a newborn girl with several dysmorphic features and
cardiac problems, suspected for Jacobsen syndrome. Cytogenetic
analysis showed a 46,XX,del(11)(qter) karyotype, which was confirmed
by fluorescence in situ hybridization (FISH). Cytogenetic investigation
of the parents showed a chromosome aberration in both:
the father presented a t(11;12)(p13;q22) and the mother was carrier
of an ins(4;11)(p14;q24q25). Additional FISH analysis with BAC
probes from chromosome 11q23.3-q25 showed that the maternal
ins(4;11)(p14;q24q25) was in fact the result of two subsequent events:
first, a small inversion in the long arm of one chromosome 11, and
second, an insertion of a small distal part of the long arm of the inverted
chromosome 11 into the short arm of one chromosome 4. Therefore,
the maternal karyotype was revised into 46,XX,der(4)(4pter→
4p14::11qter::11q24.1→11q25::4p14→4qter),der(11)(pter→q23.3::
q25→q25:). The karyotype of the newborn girl was accordingly rewritten
as 46,XX,der(11)(pter→q23.3::q25→q25:)mat.
The aberrant karyotypes in both parents implicated an increased risk
of unbalanced fetal chromosome composition, and thus a high risk
for a child with multiple congenital abnormalities. Therefore, during
the next pregnancy, the couple opted for invasive prenatal diagnosis
by amniocentesis. To obtain an early indication of the expected fetal
karyotype, an interphase FISH strategy for uncultured amniotic fluid
cells was designed. Karyotyping of cultured amniotic cells confirmed
one of the two predicted cytogenetic options, demonstrating the importance
of an interphase strategy for couples with both parents being
carrier of a chromosomal abnormality.
P0353. Jumping translocation and Prader-Willi syndrome: about
one case
F. Girard 1 , B. Doray 2 , S. Soskin 3 , V. Biancalana 4 , M. Fradin 1 , N. Carelle 1 , C.
Joumard 1 , E. Flori 1 ;
1 Service de cytogénétique, CHRU de Strasbourg, Strasbourg, France, 2 Service
de génétique médicale, CHRU de Strasbourg, Strasbourg, France, 3 Service de
pédiatrie 1, CHRU de Strasbourg, Strasbourg, France, 4 Laboratoire de diagnostic
génétique, CHRU de Strasbourg, Strasbourg, France.
Jumping translocations are rare chromosomal events and are defined
as chromosome rearrangements involving a donor chromosome segment
which is translocated to various receptor chromosomes.
The majority of jumping translocations have been observed in haematological
malignancies.