2008 Barcelona - European Society of Human Genetics

Cytogenetics
Facultad de Medicina, Universidad Complutense., Madrid, Spain.
Terminal inversion duplications (inv dup) are relatively uncommon . The
most frequent and well characterized inv dup, involved the 8p, where a
maternal heterozygous inversion between the two OR gene-clusters,
are causally related to the inv dup, and has always associated a terminal
deletion and an intact segment 8p .
Here we describe a female patient with a dicentric inversion duplication
4p without any apparent euchromatin deletion .
The patient was a female newborn, first daughter of a young, healthy
and non-consanguineous couple . Pregnancy was uneventful, until the
37th gestational week when a maternal hypertension was diagnosed .
The delivery was induced at 38 weeks . At birth she showed microcephaly,
a right cephalohematoma, craniofacial anomalies and skeletal
anomalies of hands and feet .
High resolution G-band karyotype from peripheral blood lymphocytes,
revealed a “de novo” 4p+ chromosome . FISH analyses with 4p probes,
showed that the extra material on 4p was a dicentric inverted duplication
(cen-p16 .3::p16 .3-qter) .
We postulate that a chromatic breakage could have happened at the
very terminal end of the chromosome 4, losing the common telomeric
region (-TTAAGGG-) but saving the subtelomeric specific region. This
was followed by U-type reunion producing a dicentric chromosome,
which after a break at a centromeric region, gave rise to the abnormal
dic inv dup 4p chromosome . The abnormal 4p was afterwards stabilized
by the addition of a new -TTAAGGG- repeat sequence mediated
by the telomerase, but surprisingly this sequence was internal to the
centromere sequence .
Acknowledgements: This work was supported by a Grant PI020028
(FIS) . CIBERER, ISCIII . Spain .
P02.138
DNA methylation patterns of extra chromosomes in chorionic
villi cells of missed abortions
O. A. Efimova 1 , M. A. Andrushuk 1 , A. A. Pendina 2 , O. G. Chiryaeva 2 , L. I. Petrova
2 , N. A. Sadik 2 , V. S. Dudkina 2 , T. V. Kuznetsova 2 , V. S. Baranov 2 ;
1 Saint-Petersburg State University, Saint-Petersburg, Russian Federation, 2 Ott’s
Institute of Obstetrics and Gynecology, Saint-Petersburg, Russian Federation.
Distribution of 5-methylcytosine (5-MeC) in human chromosomes reveals
specific MeC-banding pattern. It remains unknown whether methylation
pattern of extra chromosomes is the same as in normal euploid
cells or it bears changes of functional significance. We compared DNA
methylation patterns of extra chromosomes in cytotrophoblastic cells of
missed abortuses with abnormal and euploid karyotypes . Methylation
patterns of extra chromosomes in trisomies 9,7,13,16,17(one chorion
sample for each case), in triploidy(three samples) and tetraploidy(one
sample) as well as structurally rearranged chromosomes were studied
on direct metaphase preparations from cytotrophoblast of human
missed abortuses at 5-8 weeks of gestation .
Indirect immunofluorescence with monoclonal antibodies
(Eurogentec,Belgium) was applied to detect chromosome regions, enriched
in 5-MeC . No difference of 5-MeC signal distribution along chromosomes
and its intensity between normal and aneuploid/polyploid
cells was detected . In either case, 5-MeC-rich sites corresponded to
T-,R-bands, short arms of acrocentrics and heterochromatin of chromosomes
1,9,16 . Methylation intensity in homologues differed only in
9q12 and 16q11 (heterochromatin) in triads and tetrads .
DNA methylation pattern in structurally rearranged chromosome 7
(47,XX,i(7)(q10),+i(7)(p10)) was studied . The pattern 5-MeC signal
distribution in both der(7) was band-specific and did not differ from that
of the structurally normal one, as well as from homologues in normal
karyotype .
Thus, methylation pattern in extra copies of normal and rearranged
chromosomes is identical to that in normal karyotypes . Different methylation
of 9q12 and 16q11 in homologues is more probably due to special
role of heterochromatin in cytotrophoblast cells rather than change
of methylation in aberrant karyotypes .
Supported by CRDF&RFBR .
P02.139
Unusual clinical manifestations Associated with Down
syndrome
H. Mutlu, M. Ture, S. Sarısoy, S. Sarısoy, K. Baysal, F. Ekici, B. Ozyilmaz, C.
Celenk, G. Ogur;
Ondokuz Mayis University Medical Faculty, Samsun, Turkey.
Down syndrome(DS) is by far the most common and best known chromosomal
disorder .The cause is full trisomy 21 in the majority patients
(94%) . Mosaicism (2 .4%) and translocations (3 .3%) account for the
rest . Most unbalanced translocations are de novo (75%), and the rest
result from familial translocation . Here we report 3 cases of Down Syndrome
presented with unusual clinical findings.
CASE 1: 3-month-old infant with DS was cytogenetically diagnosed as
translocation type “der(13;21)” resulting from a Robertsonian translocation
of the mother. Radiological evaluation confirmed an asymptomatic
Morgagni Hernia .
CASE 2: 18-month-old DS patient presented with cleft lip-palate .
Karyotype revealed regular Trisomy 21 .
CASE 3: Cytogenetical analysis of a 2-month-old infant presenting DS
showed 47,XY,+21 karyotype . Physical examination revealed a female
external genitalia and inguinaly located bilateral gonads . Ultrasound
confirmed absence of uterus.
Association of DS with cleft lip/palate, Morgagni hernia and androgen
insensitivity is been rarely discussed . To our knowledge 32 cases have
been reported so far; and for androgen insensitivity assocition only 3
cases have been reffered . As up to date no androgen receptor gene
mutation has been identified in similar cases, it is yet not clear whether
this association is directly correlated . Cleft lip-palate is as well rarely
reported in DS . Coincidental occurence could thus be discussed .
P02.140
cytogenetic and parental age study of 545 cases of Down
syndrome in iran.A forty years study
M. Shariaty 1 , I. Nabipour 2 , F. Farzanfar 3 , S. Beigi 2 , M. Shariaty 1 , Z. M. Honarmand
1 , E. Daei 1 ;
1 Medical Genetics Center, Rafsanjan, Islamic Republic of Iran, 2 Persian
Gulf Health Institute, Bushehr, Islamic Republic of Iran, 3 Medical Genetics
Department,Cancer Res.Institute, Tehran, Islamic Republic of Iran.
Objective: To determine the karyotypic and maternal age profile of
Down syndrome in Iran this study started in 1965 and ended in 2004 .
Methods: 931 clinically diagnosed Down patients referred to the first
author were studied . Peripheral bloods were cultured using Leukocyte
culture method of Moorhead (1) or micro culture technique of Shariaty(
2) .Giemsa stained mitoses were analysed .Since 1975 G-banded mitoses
at the 300-450 band resolution were karyotyped
Results: Karyotypes consistent with Down syndrome were observed
in 545 patients out of 763 case .305 patients were male( 56 per cent
) and 240 cases were female(44 per cent ) .66 per cent were born in
Tehran while the rest were born across the country .Frequency of free
trisomy 21,translocation 21 and mosaics were 89 .5,5 .3 and 5 .2 per
cent respectively .the mean age of parents was 34 .67 (SD 9 .14) years
for Fathers and 28 .49 (SD 7 .71 ) for Mothers . 52 per cent of our cases
were the result of first or second pregnancies..Only 11.3 per cent had
consanguineous parents .
Conclusion: Our study of 545 cytogenetically proven Down syndrome
patients show a rather different picture regarding age of parents and
parity in mothers as compared to the western reports .In our study the
mean maternal age is 28 .4 with peak at 22 while in western countries
it is 34.Also 52 per cent of our cases are the results of first or second
pregnancies while 48 per cent are the results of 3rd to 18th pregnancies
P02.141
Pure 20q11.2 duplication: a specific behavioural phenotype?
J. Puechberty1 , G. Lefort1 , A. Schneider1 , A. Chaze1 , A. Weise2 , T. Liehr2 , H.
Starke2 , F. Pellestor1 , P. Sarda1 ;
1Service de Génétique, Hôpital Arnaud de Villeneuve, Montpellier, France,
2Institute of Human Genetics and Anthropology, Jena, Germany.
Pure 20q11 .2 duplication has only been reported once to the best of
our knowledge . We report a second case of pure 20q11 .2 duplication
in a 9 year-old-girl presenting mainly peculiar behaviour, a few dysmorphic
features and no malformations . The proposita was born to
non-consanguineous parents with uneventful histories . She was eutro-