2008 Barcelona - European Society of Human Genetics

Cytogenetics
present on the right side, but the first two pre-axial rays were present
on the left . Both elbows were abnormal with unusual upper extremities
of the radius, and lower extremities of the humerus . No other malformation
was observed even in the lower limbs . Karyotype was normal:
46,XY . At 3 years of age the patient has normal growth and psychomotor
development .
Array-CGH demonstrated in the patient a 4q34 .1 de novo deletion, encompassing
some candidate genes . Further studies are pending and
will be discussed .
P02.087
case report: Waardenburg syndrome and chromosme 13q
deletion
F. Faletra 1 , V. Petix 2 , A. Fabretto 1 , V. I. Guerci 1 , F. Marchetti 3 , F. Patarino 3 , V.
Pecile 2 , P. Gasparini 1,2 ;
1 Genetica Medica-Dipartimento Scienze e Riproduzione dello Sviluppo, Trieste,
Italy, 2 Genetica Medica, IRCCS Ospedale Infantile “Burlo Garofolo”, Trieste,
Italy, 3 Clinica Pediatrica, IRCCS Ospedale Infantile “Burlo Garofolo”, Trieste,
Italy.
Waardenburg-Shah syndrome (WS4; MIM 277580) is a disorder of the
embryonic neural crest that combines clinical features of Waardenburg
syndrome and Hirschsprung disease .The phenotype can be caused
by mutation in the endothelin-B receptor gene (EDNRB), in the gene
for its ligand, endothelin-3 (EDN3) or in the SOX10 gene .
We report a case of a 3 years old patient with hypotonia, mild psychomotor
and speech delay, and dysmorphic features . He was born a term
with a normal pregnancy . At one month he suffered of recurrent vomiting
caused by hypertrophic pyloric stenosis . During the recovery were
found also abnormal values of γGT and transaminases. The ERCP
and biopsy did reveal any hepatic involvement neither biliary obstruction
. Moreover, a NMR was performed because of hypotonia and
mental retardation and corpus callosum agenesis was evidenced . An
ABR exam revealed also a monolateral sensorineural hypoacusia . The
patient presents with heterochromia irides, wide nasal bridge, short
nose with smooth philtrum, mild retrognatia and legs’ hypopigmented
skin patches . For the clinical signs a syndrome was suspected and a
standard karyotype was performed . The analysis indicate an interstitial
deletion of the long arm of chromosome 13. To better define the chromosomal
anomaly we performed a CGHArrays . The result showed the
presence of a 12,5 ± 1,9 Mb deletion at 13q31 .1 à q21 .32 region . The
deletion involves the EDNRB gene, linked to WS4 . Because of the
presence of the other signs that don’t fit with WS4 phenotype, we are
trying to correlate the clinical features with the deleted genes .
P02.088
Prenatal detection of an interstitial 10p deletion: case report
L. Lecerf1 , S. Whalen1 , J. Levaillant2 , N. Chevalier2 , L. Druart3 , M. Portnoï4 , M.
Goossens1 , I. Giurgea1 ;
1 2 INSERM U841, Hôpital Henri Mondor, Créteil, France, Service de gynécologie-obstetrique,
Centre Hospitalier Intercommunal de Créteil, Créteil, France,
3 4 Dpt de cytogénétique, Laboratoire LCL, Paris, France, Dpt de cytogénétique,
Hôpital Trousseau, Paris, France.
Background: Partial 10p monosomy is a rare chromosomal abnormality,
with approximately 50 reported patients . Phenotypic spectrum
of patients with chromosomal rearrangements of that region is
wide. A critical haploinsufficiency region for DGS/VCFS (ressembling
Di George syndrome) has been described in certain patients with
10p13p14 deletion . This region encompasses two different loci, HDR1
(hypoparathyroidism, deafness, renal dysplasia) and DGCR2 (cardiac
defect, T cell deficiency), but the phenotype-genotype correlation is
not clear . No cases of deletions more proximal that these loci have
been reported .
Case report: We report a prenatally diagnosed interstitial deletion of
10p in a male patient . Antenatal karyotype was undertaken after cerebral
ventriculomegaly and ventricular septal defect (VSD) were detected
. An interstitial 10p deletion was diagnosed, with normal FISH
of DGCR2 locus . Few days later, the patient was born, at term, with
normal growth parameters . At 13 months of age, growth was on -1 .5
SD with postnatal microcephaly . He had delayed psychomotor development,
axial hypotonia and peripheral hypertonia . Facial dysmorphia
included bilateral ptosis and epicanthus, anteverted nares, dysplastic
ears and Cupid’s bow upper lip . Severe bilateral deafness, perimembranous
VSD, bilateral cryptorchidy, chorio-retinal coloboma and toe
camptodactyly and syndactyly were noted . Brain MRI showed ventriculomegaly,
cerebellar hypoplasia and bilateral anterior optic nerve
hypoplasia . Array CGH was performed after birth in order to determine
the precise 10p deletion, and revealed a proximal deletion: 10p11 .2p12
.1 .
Conclusion: We report a patient with prenatally detected unreported
proximal interstitial 10p deletion, with multiple congenital abnormalities,
including conotruncal cardiac malformation, deafness, cerebral
malformations and specific dysmorphia.
P02.089
molecular cytogenetic characterization of an interstitial
14q24q32 deletion in a girl with corpus callosum hypoplasia
i. ouertani1 , m. chaabouni1 , l. kraoua1 , f. maazoul1 , i. chelly1 , l. ben jemaa1 , m.
le lorch2 , h. chaabouni1 ;
1 2 department of congenital and hereditary disorders, tunis, Tunisia, department
of cytogenetics, embryology and feotopathology, paris, France.
Interstitial deletions of 14q including the q31 region are uncommon .
Only 15 cases were reported .
We report on a 3 year-old Tunisian girl with an interstitial deletion of the
long arm of chromosome 14 diagnosed by standard karyotype .
The girl presented with dysmorphic features, developmental delay and
hypoplasia of corpus callosum . Using Fluorescent In Situ Hybridization
technique (FISH), we characterized the deletion boundaries corresponding
to the Bacterial Artificial Chromosomes (BAC): RP11-501I4
and CTD2348N10 .
The karyotype was interpreted as46,XX,del(14)(q24 .3q32 .2) covering
nearly 24Mb .
Our patient shares with the previously reported 14q31 deletions some
similar features such as microcephaly, hypotonia, ears abnormalities,
strabismus, hypertrichosis and carp mouth .
She presents a corpus callosum hypoplasia on cerebral MRI which the
first time reported in association to such deletion.
However, the hypoplasia of corpus callosum is described only in our
patient . We propose that the deled region in our patient could present
a candidate gene for this cerebral abnormality .
P02.090
A 0.43 mb region within the 1q44 commonly deleted in three
patients with microcephaly and agenesis of the corpus callosum
A. Caliebe 1 , J. I. Martin-Subero 1 , J. J. S. van der Smagt 2 , H. Y. Kroes 2 , R. van ’t
Slot 2 , R. J. Nievelstein 3 , K. Alfke 4 , U. Stephani 5 , R. Hochstenbach 2 , R. Siebert 1 ,
M. Poot 2 ;
1 Institute of Human Genetics, Kiel, Germany, 2 Department of Medical Genetics,
Utrecht, The Netherlands, 3 Department of Pediatric Radiology, Utrecht, The
Netherlands, 4 Department of Neuroradiology, Kiel, Germany, 5 Department of
Neuropediatrics, Kiel, Germany.
Complex congenital phenotypes involving mental retardation and
developmental delay frequently result from structural genome aberrations
such as interstitial or subtelomeric microdeletions . Although
some of these aberrations may lead to recognizable phenotypes, a
high degree of phenotypic variability often complicates a comprehensive
clinical and genetic diagnosis . We describe three patients who
share developmental delay and mental retardation, including retarded
development and limited speech abilities, hypotonia, febrile seizures or
epilepsy, hypertelorism, an abnormal corpus callosum and other CNS
anomalies . By high resolution oligonucleotide and SNP array-based
segmental aneuploidy profiling we detected in chromosomal region
1q44 three overlapping deletions of 1 .250, 4 .210 and 9 .436 Mb in size .
The three patients share a 0 .43 Mb interstitial deletion, which contains
the FAM36A, HNRPU and the EFCAB2 genes . This region does not
contain AKT3 and ZNF238, two previously proposed candidate genes
for microcephaly and agenesis of the corpus callosum . Therefore, we
conclude that the HNRPU gene, which is deleted in all deletion 1q44
patients reported thus far, may represent an additional candidate for
the core features of the terminal 1q deletion syndrome . Since only one
of the two patients with deletions including the ZNF124 gene showed
a Dandy Walker Malformation, mere hemizygosity for this gene seems
not to be sufficient to cause this anomaly.
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