2008 Barcelona - European Society of Human Genetics

Cytogenetics
(according to questionnaire) volunteer donors by bone marrow aspiration
. To test genome stability, we performed karyotyping by QFH-banding
technique with AcD-counterstaining .
First, we made a comparative analysis of hMSC karyotype with that of
relevant dcPHA-stimulated lymphocytes, cultured under standard conditions
. Lymphocytes demonstrated normal male or female karyotypes
in either donor . Comparative analysis of metaphase chromosomes
showed perfect karyotype concordance in both hMSC and lymphocytes
.
Second, we analyzed hMSC karyotype at early passages - from 4 to
7 . Metaphase chromosomes were obtained by colchicines treatment 5
hours before fixation; 8-15 metaphases were selected for karyotyping
in each case . No differences in hMSC karyotype among cells of the
same culture as well as among cells from cultures after different passages
could be detected . No aneuploid or polyploid cells as well as no
cells with structural chromosome rearrangements were registered .
Thus, no adverse effect of cell passaging on chromosome number or
their morphology could be detected, advocating for genome stability of
hMSC at early passages .
Supported by RFBR .
P02.152
Familial chromosome 9 balanced intrachromosomal insertion
leading to offspring with A 9Q34
F. Girard 1 , N. Carelle-Calmels 1 , C. Joumard 1 , A. Bazin 2 , P. Kleinfinger 2 , H.
Freysz 3 , E. Flori 1 ;
1 Hopital de Hautepierre, Strasbourg, France, 2 Laboratoire Pasteur-Cerba,
Cergy-Pontoise, France, 3 Centre Hospitalier de Sélestat, Sélestat, France.
Shifts or intrachromosomal insertions represent very rare complex
three-break rearrangements. They are classified in peri- or paracentric
insertions depending on their occurrence within one or two arms . They
can be direct or inverted depending on the orientation of the inserted
segment with regard to the centromere . The normal carriers have a
high reproductive risk .
We report on a family with a chromosome 9q paracentric insertion discovered
through a newborn male referred for cytogenetic analysis because
of the association of facial dysmorphism, radio-ulnar synostosis,
undescended testes and hydronephrosis . A recombinant chromosome
9 was found . Parental karyotypes showed a paternal intrachromosomal
insertion of a part of 9q34 band . By using molecular cytogenetic
techniques (CGH-array and FISH), we characterized the break points
of the insertion . After chromosomal study of the family, four other carriers
of the insertion were found . A prenatal diagnosis could be proposed
to a pregnant woman whose husband was a normal carrier and
a 56 year old woman with an unexplained abnormal phenotype was
identified as a carrier of the recombinant chromosome 9.We discuss
the mechanism which have led to this duplication .
P02.153
Paternal origin of a large inv dup(15) supernumerary marker: no
abnormal phenotype at 2 years old
a. guichet 1 , p. boisseau 2 , o. ingster 1 , s. beziau 2 , d. bonneau 1 ;
1 service de genetique, angers, France, 2 service de genetique, nantes, France.
Inv dup(15) can be classified into 2 major groups according to size, determined
by presence or absence of Prader -Willi/Angelman syndrome
critical region (PWACR) . Small inv dup (15), not containing PWACR
seems to have no phenotypic effect where as large ones, containing 2
or more extra copies of the 15q11q13 region, are associated with abnormal
phenotype . In those cases, inv dup(15) are maternal in origin .
We report on a prenatal observation with a mosaic marker confirmed
after birth . The proband is the second child of a young, healthy and
unrelated parents . Prenatal diagnosis performed due to increased fetal
nuchal translucency at 22 weeks of gestation indicated cytogenetic
mosaicism for a supernumerary marker . The low level of mosaicism
did not permit to identify it: 47,XX,+mar[3]/46,XX[52] .Normal karyotypes
were found in both parents .
After birth, the karyotype was analysed on different tissues and all confirmed
mosaicism for the marker: 45% for blood sample and 25%for
fibroblasts. FISH studies with commercial probes and BACs probes
from 15q11q13 region allowed us to characterize the marker as an inv
dup (15)(q11q12) including the Prader-willi/angelman critical region .
Moreover, molecular studies for parental origin demonstrated a paternally
derived inv dup (15) .
At 2 years old the young girl has a normal phenotype with no dysmorphic
features and no psychomotor retardation .
Conclusion: we report on a young child with a large mosaic inv dup(15)
whose paternal origin was rarely reported and supposed to be the explanation
for the good psychomotor development of this child .
P02.154
the recurrence of pericentric inversions of chromosome 12 in
the tunisian population
R. Louati 1 , F. Kallebi 1 , R. Frikha 1 , M. Meddeb 2 , T. Rebai 1 , N. B. Abdelmoula 1 ;
1 Medical University, Sfax, Tunisia, 2 Laboratory of Genetics, Tunis, Tunisia.
We report a recurrent pericentric inversion of chromosome 12 in five
Tunisian families . It was ascertained through cytogenetic analysis of 3
men investigated before ICSI treatment for idiopathic infertility and two
sisters explored because of IVF attempts failure and recurrent early
pregnancy losses. The fifth family was ascertained through a prenatal
diagnosis because of a familial history of a chromosome 12 inversion
in an infertile female member . In these families, there was no familial
occurrence of patients with mental retardation or multiple congenital
anomaly syndromes, suggesting that unbalanced recombinations
seem to be lethal . The same inv(12) was reported by other Tunisian
cytogenetic laboratories, in association with infertility or recurrent abortions
.
These pericentric chromosome12 inversions have two different breakpoints:
inv(12)(p11q12) shown in three families originated from Sfax
town and inv(12)(p12q11) revealed in two families originated from suburbs
of Sfax town .
This inversion may have an independent occurrence from different
ancestors or has been transmitted from a common founder . Further
more, observation of 2 different breakpoints can be explained by genomic
structure of chromosome 12 which contains numerous duplicated
and repetitive sequence elements that could mediate the formation
of this recurrent inversion . We propose that pericentric inversion of
chromosome 12 is a recurrent observation in Tunisian population and
need characterization of breakpoints at the molecular level, to ascertain
whether the formation of the inversion is mediated by repetitive
sequence elements and haplotype analysis, to determine the proportion
of inv(12)s that arose independently and the proportion that share
an ancestral founder .
P02.155
Unexpected prenatal detection of recombinant chromosomes
derived from pericentric inversions: report of two cases
C. Morales1 , A. Soler1,2 , J. Bruguera3 , I. Mademont4 , E. Margarit1,2 , A. Sánchez1,2
;
1Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain,
2 3 IDIBAPS, Barcelona, Spain, Fundació Clínic per a la Recerca Biomèdica,
Barcelona, Spain, 4CIBERER, Barcelona, Spain.
Pericentric inversions, excluding variant forms, are rare chromosomal
abnormalities and have an estimated frequency ranging from 0 .12%
to 0 .7% . During meiosis, recombination could lead to the formation
of unbalanced recombinant (rec) chromosomes . Two alternative recs
are possible: duplication of q-arm and deletion of p-arm or duplication
of p-arm and deletion of q-arm . The probability of recombination
increases with the size of the inverted segment . However, the viability
of the recombinants depends on the length of the non-inverted segments
. We report two prenatal diagnoses of fetuses with recombinant
chromosomes resulting from parental inversions recently detected in
our laboratory . Case 1: CVS was performed on a 30-year-old pregnant
due to edema, increased nuchal translucency and suspicious of
cardiopathy . The karyotype showed a derivative chromosome 14 with
partial deletion of q-arm . Subtelomeric MLPA showed 14qter deletion .
Cytogenetic analysis of the mother showed that she was carrier of an
inv(14)(p11 .1q24) . The pregnancy was terminated and the pathological
examination confirmed tetralogy of Fallot. The karyotype of the fetus
was described as 46,XY,rec(14)dup(14p)inv(14)(p11 .1q24)mat . Case
2: CVS was performed on a 32-year-old pregnant due to increased
nuchal translucency and positive screening for Edwards’s syndrome
(1/10) . Cytogenetic analysis showed extra material on chromosome
4p . Subtelomeric MLPA showed 4pter deletion and 4qter duplication .
After karyotyping the parents, the father proved to be carrier of an
inv(4)(p15 .3-p16q33), so the karyotype of the fetus was described as
46,XX,rec(4)dup(4q)inv(4)(p15 .3-p16q33)pat . First trimester cytoge-