2009 Vienna - European Society of Human Genetics

Cytogenetics
que, CHU Amiens, Amiens, France, 3 Service de Génétique Médicale, Hôpital
Jeanne de Flandre, Lille, France, 4 Laboratoire de Cytogénétique, CHU Amiens,
Amiens, France, 5 Service de Biochimie et Génétique, INSERM 841, IFR10
- Institut Mondor de, Créteil, France.
Familial thrombocytopenia (OMIM 601399) is a rare inherited disorder
due to mutations in the RUNX1 gene, localized in 21q22.12. Affected
individuals have mild to moderate thrombocytopenia and are
prone to develop myelodysplasia and acute myeloid leukaemia in 1/3
of cases. Deletions including the RUNX1 gene have been reported in
patients presenting with syndromic thrombocytopenia. We report two
new cases, a 23 year-old boy and a 7 year old girl. Both developed
mild asymptomatic thrombocytopenia. Psychomotor development was
severely delayed and both developed severe epilepsia and behavioral
problems with agitation and restlessness. On examination the two
patients had dysmorphic features, with microcephaly, protruding and
everted lips, down turning corners of the mouth and bulbous nasal tip.
Hypoplastic nipples, short fingers with broad proximal interphalangeal
joints, camptodactyly, broad halluces, toenail hypoplasia and complete
agenesis of corpus callosum were noted in the male patient. Deletions
at 21q22.11q22.12 including RUNX1 were detected by array-CGH in
the two cases. The two deletions overlapped with distinct breakpoint.
Recently, genomic deletions overlapping the 21q22.11q22.12 region
were reported in 5 patients. All had thrombocytopenia, growth retardation
and mental retardation and one developed AML. The facial appearance
of the three patients with published pictures is very similar
to the one of our patients. Interestingly, the size of the deleted region
is variable and breakpoints are specific to each patient, suggesting a
mechanism different from the classical non-allelic reciprocal recombination.
The minimal overlap region contains 13 genes, some of which
are expressed in the central nervous system.
P03.079
Duplication of the GPc3/GPc4 gene cluster on Xq26.2 detected
by Array-cGH in a family with developmental delay/mental
retardation and dysmorphic features. A new syndrome ?
H. Gabriel1 , E. Fiedler2 , A. Lott1 , A. Ovens-Reader2 , M. Gencik1 , G. Strobl-
Wildemann2 ;
1 2 Zentrum fuer Medizinische Genetik, Osnabrueck, Germany, Praxis für
Humangenetik, München, Germany.
Simpson-Golabi-Behmel (SGBS) syndrome is an X-linked overgrowth
syndrome characterized by pre- and postnatal overgrowth, a characteristic
facial appearance and different congenital malformations. SGBS
is caused by mutations or deletions of the glypican 3 (GPC3) gene.
Here, we report on a 2-year-old boy presented with pychomotoric retardation,
growth retardation, microcephaly, mild congenital malformations
(micropenis, hypospadia) and dysmorphic features (e.g. broad
forehead, facial asymmetry, round face, hypertelorism, micrognathia,
deep set and posteriorly rotated ears, slight bilateral clinodactyly).
Initially, Silver-Russell-syndrome was suspected. While karyotyping
and testing for Silver-Russell syndrome were negative, a 1-4 Mb duplication
at Xq26.2 including the GPC3/GPC4 gene cluster was identified
by BAC array-CGH. This finding was validated by MLPA and Q-PCR
analysis.
For the characterization of the duplication in a much higher resolution
we have designed and customized a 60mer oligo array printed
in a 105K format (105.000 oligonucleotides probes) using the eArray
technology (Agilent).
Testing of more family members revealed that the mother, the grandmother
and a maternal uncle were carrier of the Xq26.2 duplication.
All carriers displayed the characteristic features of the syndrome to
some extent.
Interestingly, comparison of the Xq26.2 duplication phenotype to the
phenotype of SGBS patients revealed partially a “reverse” phenotype
to the SGBS.
Recently, it was proposed that the SGBS phenotype is caused by a
misregulation of the hedgehog signal transduction pathway. Here we
will present a potential explanation of the phenotypical differences between
the two syndromes based on the function of glypican 3 in the
hedgehog signal transduction pathway.
P03.080
De novo cryptic deletion at 2q14 in two female patients with
turner syndrome stigmata
S. Giglio1,2 , R. Ciccone3 , I. Ricca4 , E. Andreucci1 , M. Patricelli5 , S. Guarducci2 ,
E. Della Mina3 , O. Zuffardi3,6 ;
1 2 Medical Genetics- Dept of Clinical Pathophysiology, Florence, Italy, Medical
Genetics Unit, Meyer Children’s University Hospital, Florence, Florence, Italy,
3 4 Medical Genetics, University of Pavia, Pavia, Italy, Genetics Unit- C. Mondino
Foundation, Pavia, Pavia, Italy, 5Clinical Genetics-San Raffaele Hospital, Milan,
Milan, Italy, 6Genetics Unit- C. Mondino Foundation, Pavia, Italy.
Case1. 13 years old, weight 37 Kg (3th-10th centile), height 133 cm
(