European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cytogenetics
P0285. Chromosome 22q13.3 deletion syndrome with a de novo
interstitial 22q13.3 cryptic deletion retaining SHANK
A. Delahaye1 , A. Toutain2 , A. Aboura1 , A. Tabet1 , B. Benzacken1 , A. Verloes1 ,
S. Drunat1 ;
1 2 Genetics department, Robert Debré Hospital, AP-HP, Paris, France, Genetics
department, Bretonneau Hospital, CHRU, Tours, France.
The 22q13.3 deletion syndrome (MIM 606232) is characterized by
developmental delay, absent or severely delayed speech, autistic
behavior, normal to accelerated growth, and minor dysmorphic facial
features. Among the three genes of the minimal critical region (from
centromere to telomere: SHANK3, ACR and RABL2B), SHANK3 is
considered to be at the origin of the neurobehavioral symptoms.
We report a child with a de novo interstitial 22q13.3 deletion detected
by MLPA and confirmed by FISH.
She demonstrates mental retardation, severe speech delay, epicanthic
fold, and protruding ears with normal growth. This non specific phenotype
is concordant with the classical presentation of 22q13.3 deletion
syndrome.
Subtelomeres analysis by MLPA showed a discrepancy between the
P036B and P070 kits (MCR Holland): P070 MLPA probe (targeting
ARSA gene) showed a deletion but P036B (targeting RABL2B gene)
showed a normal result. FISH analysis using LSI TUPLE1/LSI ARSA
(Vysis) probes confirmed deletion of ARSA, whereas FISH with N25/
N85A3 (Cytocell) probes, targeting SHANK3 locus was normal. This
was confirmed by quantitative real time PCR of exons 23 and 24 of
SHANK3. Supplemented FISH analysis using BAC clones were performed
to delineate both breakpoint regions of the interstitial deletion.
These data highlight the difficulty of performing an appropriate test in
order to search for cryptic 22q13.3 deletion. Furthermore the molecular
characterization of this interstitial 22q13.3 deletion contributes to
clinical and genetic delineation of the 22q13.3 deletion syndrome.
P0286. Double trisomy involving chromosome 21 and the sex
chromosome (48,XXX,+21) - a case report and literature review
R. Smigiel1 , B. Halina1 , M. Sasiadek1 , N. Blin2 ;
1Genetic Department Wroclaw Medical University, Poland, Wroclaw, Poland,
2Division of Molecular Genetics, Institute of Human Genetics, University of
Tuebingen, Germany.
Occurrence of double trisomy in the same individual is a relatively
rare phenomenon. In most cases double nondisjunction leads to an
inevitable prenatal lethality. Multiple aneuploidy, observed in live born
children usually involves sex chromosomes together with trisomy 13,
18 or 21. Multiple aneuploidy occurs as a consequence of a minimum
of two errors during meiosis. The zygote carrying a double aneuploidy
usually results from a double nondisjunction in a single germ cell
however the coincidence of a single nondisjunction occurring in both
gametes was also observed. More than 90 cases of nonmosaic trisomy
21 and numerical sex chromosome aberrations were presented
by Kovaleva and Mutton, but among them only 14 cases were diagnosed
with 48,XXX,+21. We report a case of double trisomy involving
chromosomes 21 and X in a female infant (karyotype 48,XXX,+21).
The child presented dysmorphic features such as hypotrophy, microcephaly
with a flat occiput, midface hypoplasia, up-slanting palpebral
fissures, epicanthic folds, low set ears, open mouth with macroglossia
and protruding tongue, short neck, small hands and feet, simian
creases, wide space between first and second toes, a umbilical hernia,
dislocated hips, congenital heart defect, a mild hearing loss and hypothyroidism.
The observed dysmorphic features as well as other deformities
are consistent with those characteristic for trisomy 21. However,
genetic counselling in such cases is difficult. Neither data concerning
the clinical outcome of the double trisomy children nor any information
concerning the recurrence risk for their parents exist to date.
P0287. Delineation of the deletion breakpoints in two unrelated
patients with 4q terminal deletion syndrome
S. S. Kaalund 1 , R. S. Møller 1,2 , A. Tészás 3 , M. Miranda 2 , H. H. Ropers 4 , R.
Ullmann 4 , N. Tommerup 1 , Z. Tümer 1 ;
1 Wilhelm Johanssen Centre for Functional Genome Research, Department
of Cellular and Molecular medicine, University of Copenhagen, Copenhagen,
Denmark, 2 Danish Epilepsy Centre, Dianalund, Denmark, 3 Department of Medical
Genetics and Child Development, University of Pécs, Hungary, 4 Max Planck
Institute for Molecular Genetics, Berlin, Germany.
INTRODUCTION: Deletion of the terminal region of the long arm of
chromosome 4 results in a series of clinic features including developmental
delay, cleft palate and limb defects. Due to the similarities of
the clinical symptoms a 4q-deletion syndrome has been suggested.
This study aims to find the critical region responsible for the 4q-deletion
syndrome through fine mapping the terminal 4q deletions in two
unrelated patients.
METHODS: The patients were analysed using array CGH and FISH.
Array CGH was carried out using a submegabase resolution whole
genome tiling path BAC array and the results were verified by FISH
analysis, using standard protocols.
RESULTS:
The 4q terminal deletions of two patients with cleft palate, limb defects
and developmental delay were fine mapped using array-CGH.
Both deletions were positioned at 4q33-4qter. Furthermore, one of the
patients displayed a cryptic unbalanced translocation between chromosome
4 and chromosome 20, resulting in the loss of 4q33-4qter
and trisomy of the 20p13-20pter region. The chromosomal aberrations
were de novo in both patients.
CONCLUSION: In the present study we investigated two patients with
deletion of the terminal long arm of chromosome 4. Our data support
that 4q33 may be the critical region for the 4q-syndrome. This study
also underlines the power of array-CGH in identifying cryptic unbalanced
translocations.
P0288. Clinical aspects of the deletion 9p syndrome - two new
cases
E. Braha, M. Volosciuc, I. Ivanov, A. Sireteanu, M. Covic;
University of Medicine and Pharmacy, Iasi, Romania.
Nearly 100 cases of deletion 9p has been published. Often, the deletion
occurs de novo. We reported two unrelated children who share
particular clinical findings including trigonocephaly, microstoma, hypotelorism,
broad nasal root, upslanted fissures, motor retardation. One
patient has a congenital cardiac anomaly (VSD and PDA). Family history
did not reveal any other family members with similar findings or
different congenital anomalies.
The similar findings of these cases suggested a chromosomal disorder.
Cytogenetic investigation demonstrated del(9)(p22->pter) in both
cases. The chromosomal analysis for parents are in progress.
The first patient has a number of clinical findings invariably found in
the 9p- syndrome. However, the other patient has a partial optic nerve
atrophy which has not been reported before.
P0289. Cytogenetic, morphologic and immunophenotypic
pattern in omani patients with de novo acute myeloid leukemia
A. M. Udayakumar1 , A. Pathare2 , S. Alkindi1 , H. Khan2 , J. Ur Rehman2 , F. Zia2 ,
A. Al Ghazaly2 , N. Nusrat2 , I. Khan2 , M. Zachariah2 , Y. Wali1 , D. Dennison2 , J.
Raeburn1 ;
1 2 College of Medicine & Health Sciences, Muscat, Oman, Sultan Qaboos University
Hospital, Muscat, Oman.
Objective: To characterize the cytogenetic, morphologic and immunophenotypic
pattern in ethnic Omani patients with de novo Acute Myeloid
Leukemia (AML).
Material and Methods: Successful cytogenetic results were obtained
from 63 de novo AML patients. Forty-one were male and 22 female
with a median age of 25 years. Chromosomes were obtained by shortterm
cultures and interpreted after G-banding. The diagnosis of AML
was based on French-American-British (FAB) cytomorphology criteria
& the immunophenotyping of bone marrow.
Results: Karyotypic abnormalities were present in 39 patients(61.9%)
with 44.2% in adults and 17.7% in children. Karyotypes with sole abnormalities
amounted to 31.7%(n=20). Chromosomal abnormalities
were more common in patients with FAB-M2 subtype (n=22;68.2%).
The most frequent subtype observed was M2 (n=22;34.9%). Among
the normal karyotypes (n=24;38.1%) M2 -subtype was again the most
frequent (n=7;29.2%) followed by M4(n=4;16.67%). Among balanced
translocations t(8;21) and t(15;17) were observed in 11.1% and 9.5%
respectively. Inv(16) was seen in 3.2%. Trisomy 8 was the most frequent
numerical anomaly found in 11.1%. Monosomy 7 was seen 4.7%.
Discussion: This is the first systematic cytogenetic report from the ethnic
Omani population [1.78 million] studied over the last 5 years from
a single institution. We observed that findings in our study were similar