2008 Barcelona - European Society of Human Genetics

Cytogenetics
chromosomal aberration. In some cases, for identification or confirmation
of detected abnormalities, specific microdeletion and telomeric
probes were used .
Results: Twelve subtelomeric chromosomal aberrations were recognized,
which corresponds to a diagnostic yield of about 10% .
Identified rearrangements were: del(1p36); der(1)t(1;3)(q44;p2
5)pat; der(1)t(1;22)(p36 .1;q11 .23)mat; del(2q37) in two cases;
del(4p); der(6)t(6;7)(q27;q36)mat and der(7)t(6;7)(q27;q36)mat;
der(9)t(9;20)(pter-,pter+)pat; del(9qter); del(12pter); del(22q13) .
Conclusions: Since there is still limited knowledge of the phenotype of
many subtelomeric aberrations, we believe that our study gives insight
into the etiology of mental retardation by clinical delineation of subtelomeric
aberrations .
The work was supported in part by grant KBN 2P05A 161 28
P02.004
telomeric submicroscopic Deletion of chromosome 1
E. Gean 1 , V. Catala 2 , I. Plensa 3 , C. Garrido 2 , A. Garcia-Cazorla 1 , Y. Jordan 1 , D.
Velasco 1 , P. Poo 1 ;
1 Hospital sant Joan de Deu, Esplugues. Barcelona, Spain, 2 Prenatal Genetics,
Barcelona, Spain, 3 Hospital Sant Joan de Deu, Esplugues. Barcelona, Spain.
Submicroscopic deletion 1ptel the most common telomeric deletion
with an incidence of 1:5000 live births . Patients carrying this deletion
tend to have similar phenotypes . We describe 3 patients with 1ptel
deletion .
Case 1: Female, 3 years old, is an only child born to healthy unrelated
parents . Pregnancy was normal . Clinical examination: dystrophic appearance
. Microcephaly . Synophrys and dull face . General hirsutism
and severe developmental delay .
Case 2: Female, 13 year old, first chills of healthy and non consanguineous
parents .
Growth retardation and early puberty, pulmonary stenosis, sensorineural
hearing loss and moderate mental retardation . Facies was characteristic
of 1ptel deletion .
Case 3: Male, 2 month old, with congenital cardiac anomaly and facial
dysmorphic features: facial hirsutism, short palpebral fissures and developmental
delay .
In all the patients FISH analysis showed deletion 1p36 .3
The 1qter microdeletion is often reported in the literature as a part of
complex chromosome rearrangement. No particular feature is specifically
unique . Next, we describe 2 patients with isolated 1qter deletion
Case 1: Female, 5 years old, is an only child born to healthy unrelated
parents .
Proportioned growth retardation, congenital cardiac anomaly, pelvic
horseshoe kidney, and duodenal diaphragm . Seizures . Severe developmental
delay with facial dysmorphic features .
Case 2: Male, 8 year old, is an only child born to healthy unrelated
parents .
Clinical features: Low birth weight . New born with hypotonia and microcephaly
. Cerebellar vermis hypoplasia . Right kidney agenesis . Peripheral
pulmonary stenosis . Cryptorchid testes . Seizures and severe
mental retardation . Sterotopy . Dysmorphic features .
In both cases FISH studies showed deletion 1qter .
P02.005
Presentation of four new cases with chromosome 2q terminal
deletion
M. Elena 1,2 , M. Palomares 1,2 , P. Lapunzina 1,2 , B. Fernández 1 , I. Martínez 1 , P.
Lago 1 , J. Arcos 3 , A. Delicado 1,2 ;
1 Servicio de Genética.Hospital Universitario la Paz, Madrid, Spain, 2 Centro de
Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid,
Spain, 3 Servicio de Neurología Infantil.Hospital Universitario la Paz, Madrid,
Spain.
Terminal deletions of chromosome 2 may be found commonly among
patients, with idiopathic mental retardation, referred for subtelomeric
screening . Chromosome 2q terminal deletion (2q37) is characterized
by mild to moderate mental retardation, behaviour manifestations on
autism spectrum, facial dimorphism (prominent forehead, thin, highly
arched eyebrows, depressed nasal bridge, and hypoplasia nasal alae,
prominent columella and thin upper lip) and other major congenital
malformations . Patients with most distal deletion present phenotypic
features which mimic Albright hereditary osteodystrophy (AHO), including
brachymetaphalangia in nearly half of all patients .
We report four patients including for subtelomeric screening . In all
the patients a high resolution G-band Karyotype and subtelomerics
screening using MLPA were performed. Result were confirmed by fluorescence
in situ hibrization (FISH) . The four cases presented a “de
novo” terminal deletion at or within band 2q37, ranging from cytogenetically
visible abnormalities (patient 1 and 2) to cryptic subtelomerics
deletions (patient 3 and 4) . Molecular chacterization of the breakpoints
were performed by STRs . The size of the deleted segments ranged
from 2 Mb to 7 Mb .
The patient 4 showed of approximately 2Mb terminal deletion . He has
limbs abnormalities with short fourth and fifth metacarpals on the left
hand and short first, third and forth metacarpals on the right hand.
These findings are consistent with previous observations to narrow the
brachydactily critical region as the terminal 3 Mb region .
We observed no clear relationship between clinical features and the
size of the monosomic region; this represents a significant difficulty in
predicting phenotype for this deletion .
P02.006
High resolution sNP-array and mLPA analyses of patients with
atypical 9q34 subtelomeric deletions
E. Van Binsbergen1 , T. Kleefstra2 , N. Verbeek1 , M. Poot1 , W. Nillesen2 , J. C.
Giltay1 , M. Nelen1 ;
1 2 University Medical Hospital, Utrecht, The Netherlands, Radboud University
Nijmegen Medical Centre, Nijmegen, The Netherlands.
Recently patients with deletions of the 9q34 region were proposed to
have a recognizable syndrome with a combination of mental retardation,
recognizable facial phenotype, hypotonia, brachy(micro)cephaly
and other congenital anomalies, mostly heart defects in up to 50% of
the cases . The EHMT1 gene has been proposed as the prime candidate
gene to be responsible for these features . In a diagnostic survey
of patients with mental retardation/multiple congenital abnormalities,
HumanHap300 illumina SNP arrays and Multiplex Ligation-mediated
Probe Amplification revealed two patients with de novo deletions in
the 9q34 region which did not include the EHMT1 gene . A patient with
moderate mental retardation and facial dysmorphologies that are also
seen in the “9q34 subtelomeric deletion syndrome” showed hemizygosity
for PNPLA7, MRPL41, WDR85, ZMYND19, ARRDC4. A second
patient with mild hydrocephalus, a heart defect (VSD) and hypospadias
but without mental retardation at the age of 5 years showed an interstitial
deletion with a maximal size of exon 3 up to 14 of the CACNA1B
gene (i .e . exon 1, 2 and 15 until 25 were not affected) . Our data (1)
emphasize the need for high resolution molecular cytogenetic analysis
to elucidate the underlying genome rearrangements in patients with
mental retardation or multiple congenital abnormalities (2) show that
EHMT1 is not the major candidate gene in all patients with a deletion
in the 9q34 subtelomeric region (3) allow further analysis of genotype
vs phenotype in larger 9q34 deletions .
P02.007
subtelomeric deletion of 1p36 detected by HR-cGH could not be
confirmed by FISH
A. Escalona1 , M. Santos1 , A. González-Meneses2 , C. Fuster1 ;
1 2 Universitat Autonoma de Barcelona, Bellaterra, Spain, Hospital Virgen del
Rocío, Sevilla, Spain.
Background Molecular High Resolution Comparative Genome Hybridization
(HR-CGH) is applied to detect an imbalance in whole genome .
This technique is especially successful in detecting small genomic
abnormalities in patients with unexplained mental retardation and/or
congenital malformations .
Objective To detect and identify the existence of any chromosome
alteration in two unrelated girls with mental retardation and multiple
congenital clinical features .
Methodology G-banding, HR-CGH and FISH .
Results Conventional GTG-banded chromosome analyses revealed a
normal karyotype in both cases . Analysis by HR-CGH demonstrated
a loss in 1p36 in two patients. However, FISH with a specific subtelomeric
1p probe detected 1pter deletion in only one patient .
Conclusion Our results showed that a combination of both CGH and
FISH should always be used in the identification of 1p36 microdeletion,
which is difficult or impossible by banding techniques alone
ACKNOWLEDGMENTS: This work was supported by MCYT (SAF
2003-03894) and CIRIT (2005, SGR-00495) .