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

Cytogenetics
affected family members. The study included genotype-phenotype correlations
and thus, contributed to clinical and molecular characterization
of subtelomere aberrations. We showed the usefulness of recently
developed technology for accurate diagnosis of submicroscopic chromosome
abnormalities and their application in genetic counselling.
P0423. The 4P-syndrome. A Case description and literature
review
F. Mortezapour1 , F. Mahjoubi2 , S. Soleimani1 , M. Rahnama1 , F. Razazian1 , M.
Zamanian1 , F. Manouchehri1 , F. Nasiri1 ;
1 2 IBTO, Tehran, Islamic Republic of Iran, IBTO & NRCGEB, Tehran, Islamic
Republic of Iran.
Wolf-Hirschhorn syndrome (WHS) is a rare developmental disorder
associated with deletion of short arm of chromosome 4. Well-known
genetic condition of WHS are typical facial anomalies, midline defects,
skeletal anomalies, prenatal and postnatal growth retardation, hypotonia,
mental retardation, and seizures.
Here we report a new case of WHS who referred to our clinic for cytogenetic
investigation. The patient was a 9 month old baby boy with
developmental delay, hypotonia, respiratory and heart problem, prominent
eyes and forehead and delayed bone age. GTG banded karyotype
reveald a deletion on segment of 4p (p15.31 pter). Due to a broad
spectrum of possible morphologic abnormalities followed by mental
retardation, prenatal diagnosis is very important. Postnatal recognition
of the syndrome requires genetic counseling of parents and supportive
multidisciplinary treatment.
P0424. Olfactory receptors gene clusters on 4p are not
involved in the origin of Wolf-Hirschhorn syndrome-associated
chromosome rearrangements.
G. Marangi, M. Murdolo, R. Lecce, D. Orteschi, M. E. Grimaldi, G. Neri, M.
Zollino;
Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma, Italy.
Wolf-Hirschhorn syndrome (WHS) is a multiple congenital anomalies/mental
retardation (MCA/MR) syndrome caused by partial 4p
monosomy. By analysing a total of 72 families, we found that 65 of
72 rearrangements (90 %) occurred de novo. Of these, 49 were further
analysed by all telomeres (46) or by other locus-specific FISH
(3). An isolated 4p deletion was detected in 36 (74 %), an unbalanced
translocation in 9 (18 %), a dup/del 4p in 3 (6 %), and a der(4)(4qter→
q32::4p15.3→qter) in one patient (2 %). With the purpose to investigate
if hotspots for rearrangements exist, we performed FISH analysis
with a total of 80 molecular probes, properly selected in individual
patients, spanning the 4p15pter chromosome region. In particular,
probes RP11-423D16 and RP11-751L19, delimiting the proximal OR
on 4p, and probes 228a7 and RP11-324I10, delimiting the distal OR,
were tested.
Looking at unbalanced translocations (n=16), both familial (n= 7) and
de novo (n= 9), different pattern chromosomes were diagnosed, all autosomal.
No hotspots were observed on 4p, with the exception of the
t(4p;8p) translocations, that recurred within the proximal or the distal
OR in 6 of 7 cases. Only one different de novo translocation, t(4p;7p),
did occur within the distal OR. Of the remaining 56 rearrangements,
consisting more often of isolated terminal deletions, only three were
OR-mediated. A strong relationship was observed between parental
origin and type of the de novo rearrangement. We conclude that ORs
are not usually involved in the WHS-associated rearrangements, with
the exception of t(4p;8p) translocations.
P0425. Molecular cytogenetic characterisation of an Xp
duplication in a phenotypically abnormal girl with random X
inactivation
C. Massol1 , S. Monnot1 , F. Giuliano1 , C. Fossoud2 , M. Cossée3 , J. C. Lambert1 ,
H. Karmous-Benailly1 ;
1 2 Department of Medical Genetics, Nice, France, Department of Pediatrics,
Nice, France, 3Genetic Laboratory, Strasbourg, France.
Partial duplications of the short arm of the X chromosome are relatively
rare and have been described in males and females. We report
the case of a 4 years and 10 months old girl presenting developmental
delay, severe language retardation and dysmorphic features with
macrocephaly (+1,8 SD), prominent forehead, wide palpebral fissures
and anteverted nares. No pigmentary dysplasia of the skin was present.
The external genitalia were normal. The karyotype completed by
12
cytogenetic analysis with the Whole Chromosome Painting probe of
chromosome X revealed a de novo partial duplication of the short arm
of an X chromosome.
In order to further characterize the duplicated segment, we used a
series of BAC probes extending from band Xp11.22 to Xp22.1.
BACs from Xp11.23 to Xp11.4 were duplicated. The karyotype was
finally 46,X,dup(X)(p11p11).ish dup(X)(p11.23p11.4)(WCPX+,RP11-
416I6++,RP11-386N14++,RP11-466C12++). X inactivation status was
studied using HpaII digestion of the AR and FMR1 genes. Unexpectedly,
the two X chromosomes were found to be randomly inactivated,
in the proband. Indeed, usually, in women with structurally abnormal
X chromosome, the abnormal X chromosome is preferentially inactivated
and those patients share an apparent normal phenotype. So, we
speculate that in the present case, the phenotype of the patient could
be explained by a functional disomy of the genes present in the duplicated
region. We’ll discuss the possible implication of these genes on
the observed phenotype.
P0426. Familial pericentric Y chromosome inversion in Russian
patient with trisomy 21
T. G. Tsvetkova, V. B. Chernykh, L. F. Kurilo, E. V. Il’ina, E. V. Zaklyazminskaya,
A. V. Polyakov;
Research Centre for Medical Genetics of Russian Academy of Medical Sciences,
Moscow, Russian Federation.
We reported a patient with trisomy 21 and pericentric Y inversion. The
proband, a Russian male newborn with a typical Down syndrome phenotype,
was born to a 21-y.o. G1P1 mother and an unrelated 23-y.o.
father. No genital abnormalities were mentioned in this patient.
We have examined the proband and his father, mother and grandfather.
Chromosome analysis had been carried out on peripheral
lymphocytes by standard techniques with GTG- and CBG- staining.
Genomic DNA had been extracted from peripherical leukocytes using
by standard protocol. Parents’ origin of aneuploidy had been determined
by analysis for four following polimorphic markers: D21S11,
D21S1888, D21S1890, and D21S1895. Y microdeletion analysis had
been performed using PCR amplifications for SRY, AMG/AMGL, ZFY/
ZFX loci and 21 Y-specific STSs.
The proband’s karyotype was 47,X,inv(Y)(p11.2q11.23),+21. Patient’s
father and patient’s grandfather posses the same inverted Y chromosomes,
mother had normal female karyotype. The extra chromosome
was maternal origin is to determined by molecular analysis. PCR amplifications
have shown an absence of sY1192 marker in proband and
his father and grandfather. It is typically for b2/b3 deletions, partial deletions
within AZFc region.
Remarkable, that deleted sY1192 locus falls in inverted repeat IR1 localization
near or within Yq breakpoint of pericentric Y chromosome
inversion. We suppose that revealed partial AZFc deletion may be due
to pericentric inversion in ancestor Y chromosome. The transmission
of this rearranged Y chromosome through three generations demonstrated,
that at least some partial deletions (b2/b3 deletions) even in
association with inv(Y) polymorphism not impair the male fertility.
P0427. Unbalanced translocation (Y;3) leading to 3p deletion in a
dyslexic boy and his normal mother
C. Schluth 1,2 , M. Till 1 , V. Des Portes 3 , P. Gosset 4 , V. Malan 5 , P. Edery 1,2 , D.
Sanlaville 1,2 ;
1 Service de Cytogénétique Constitutionnelle - Hospices Civils de Lyon, Bron,
France, 2 Faculté de Médecine Lyon Nord - Université Claude Bernard, Lyon,
France, 3 Service de Neuropédiatrie - Hôpital Debrousse, Lyon, France, 4 Laboratoire
de Biologie de la Reproduction - CHU Strasbourg - SIHCUS-CMCO,
Schiltigheim, France, 5 Laboratoire de Cytogénétique, Histologie et Embryologie
- Hôpital Necker Enfants Malades, Paris, France.
A 10-year-old boy was assessed for learning disability, language delay,
dyslexia and hyperactivity. He was born at 32 weeks’gestation and
required resuscitation. He walked at 19 months, suffered from frequent
otitis media and was surgically treated for hypospadias. Standard
karyotype displayed an abnormal chromosome 3 : add(3)(p25). The
same abnormality was identified on the karyotype of his phenotypically
normal mother.
FISH analyses showed that the additional material on chromosome
3p consisted of Y heterochromatin and Yq telomere. 3p subtelomeric
probe (Cytocell, 230kb from telomere) was deleted whereas the
CRELD1 locus at 10 Mb from telomere was retained. So, both mother