2008 Barcelona - European Society of Human Genetics

Cytogenetics
P02.012
High resolution oligonucleotide acGH in a Jacobsen syndrome
patient with an atypically small 6.5 mb terminal 11q deletion
supports FLi1 as an important mediator of thrombocytopenia
D. H. Tegay1,2 , H. V. Toriello3 , G. Parsons3 , E. Hatchwell2 ;
1New York College of Osteopathic Medicine, Old Westbury, NY, United States,
2Stony Brook University Medical Center, Stony Brook, NY, United States,
3Spectrum Health, Grand Rapids, MI, United States.
Jacobsen syndrome (JBS; OMIM#147791) is a MCA/MR syndrome
clinically characterized by growth and mental retardation, thrombocytopenia,
congenital heart defects, trigonencephaly and dysmorphic
facial features including telecanthus, downslanting palpebral fissures,
a broad nasal bridge and a “carp” shaped mouth . The vast majority of
reported cases are due to ~7-15 Mb de novo terminal 11q deletions
typically extending from chromosome band 11q23 to 11qter . With the
advent of high-resolution molecular karyotyping by microarray comparative
genomic hybridization (aCGH) smaller deletions are now frequently
uncovered allowing further refinement of genotype-phenotype
correlations . Here we report the case of a 5-year-old girl with clinical
features of Jacobsen syndrome including growth and mental retardation,
thrombocytopenia, and classical facial dysmorphism as well as
unilateral optic nerve hypoplasia, multicystic kidneys, aortic valve regurgitation
and a tethered spinal cord . This patient was found by highdensity
whole-genome oligonucleotide aCGH to have a small ~6 .5 Mb
chromosome 11q24 .3-qter deletion . This deletion starts just proximal
to FLI1 (friend leukemia virus integration 1) and provides additional
evidence supporting FLI1 as the important mediator of thrombocytopenia
in JBS .
P02.013
19ptel (p13.3) duplication
C. Garrido1 , E. Gean2 , V. Català1 , L. Vila1 , P. Poo2 , C. Fons2 , E. Cuatrecasas1 ,
M. Pérez2 , A. Serés1 ;
1 2 Prenatal Genetics, Barcelona, Spain, Hospital Sant Joan de Déu, Barcelona,
Spain.
Submicroscopic rearrangements involving chromosome 19 are very
uncommon, there are very few reports in the literature of patients with
partial trisomy of distal 19p . We describe two cases with 19p duplication
.
Kariotype were normal in both patients but the availability of subtelomere
specific FISH probes has made identification of cryptic subtelomeric
rearrangements possible .
case 1: Male, second child born to healthy unrelated parents, intrauterine
grow retardation (IUGR) detected in third trimester and low
weight at birth . Severe developmental delay and seizures, normal
hands and feet, and very dismorphic face .
Duplication of 19ptel using Totelvysion panel (Vysis) was observed .
The extra 19ptel signal was detected at p arm of an acrocentric chromosome
of group G .
Parents were studied and showed normal hibridization results . Duplication
of 19ptel was “de novo” in the proband .
case 2: Male, first child from non consanguineous parents, IUGR detected
in the third trimester and low birth weight . Severe developmental
delay, epilepsy and gastroesophageal reflux.
FISH studies showed a duplication of 19ptel and a deletion of 17qtel .
The extra signal 19ptel is contained within the terminal long arm of the
deleted chromosome 17q .
Parents’ studies have to be done .
P02.014
screening for subtelomeric rearrangements in mental
retardation. Description of two new cases: dup16qter and
del19qter
N. Baena1 , L. Comadran1 , I. Crespo1 , E. Gabau1 , M. Roselló2 , M. Guitart1 ;
1 2 Corporacio Sanitaria Parc Tauli, Sabadell, Spain, Hospital Universitario La Fe,
Valencia, Spain.
Copy number changes of subtelomeric chromosomal regions are responsible
for 5-10% of all mentally retarded (MR) patients . Multiplex-
Ligation Probe Amplification (MLPA) is a technology used to detect
microdeletion and microduplication syndromes .
In the current study we determined the frequency of subtelomeric
changes in a series of 108 patients showing MR and dysmorphic features
in which G banded karyotype at a 600- band level were normal .
Subtelomeric assay using MLPA with SALSA P036B/C and P070 kits,
and FISH in some cases were performed .
MLPA revealed subtelomeric changes in 9 out of 108 MR patients
(8 .3%), 7 deletions: 1p, 1q(2), 18p, 19q, 22q(2), one duplication 16q,
all of them de novo abnormalities, and one case with a concurrent
duplication and deletion 6q/3p inherited from a parental translocation
. Among these imbalances we report two rare cases . 1 .-Duplication
of chromosome 16q in a 2 -year-old girl with a pschymotor delay,
who showed intrauterine growth retardation and ventriculomegaly in
prenatal examination; plagiocephaly, delayed clousure fontanel, hypertelorism,
epicantus, small nose and mouth, tapering fingers and
hypotonia . 2 .-Deletion of chromosome 19q in a 5-year-old boy with
speech impairment and behaviour disorder, high palate and narrow
palpebral fissures.
Comparing clinical features, only one case of dup(16)(qter) (Ahn,
2007), and one case with del(19)(qter) (EUCARUCA database) reported,
both phenotypes are different from described in our patients .
These two new cases could contribute to a better clinical characterization
of these subtelomeric imbalances but more cases are necessary .
Supported by the grant from Fundació Parc Taulí of Sabadell.
P02.015
mLPA as screening method for the detection of cryptic
subtelomeric rearrangements in patients with idiopathic mental
retardation
L. Morozin Pohovski, I. Sansović, I. Barišić;
Children’s University Hospital Zagreb, Zagreb, Croatia.
Background: Submicroscopic chromosomal rearrangements involving
the subtelomere regions are considered to be a significant cause of
idiopathic mental retardation (MR) . The Multiplex Ligation dependent
Probe Amplification (MLPA) analysis has increasingly been used as
an adjunct to routine cytogenetic testing and a relatively low cost and
high throughtput screening for the deteciton of small rearrangements .
Objective: To screen for submicroscopic subtelomeric aberrations by
MLPA method . Results: We have studied a series of 50 unselected
patients with mental retardation and negative chromosomal analysis .
The MLPA with SALSA P036C and SALSA P070 probe mixes was
performed for subtelomere screening . Unbalanced chromosomal rearrangements
detected by MLPA were confirmed by quantitative fluorescent-PCR
(QF-PCR) . The MLPA screening revealed chromosome
aberrations in two (4%) cases: one patient with terminal deletion in the
long arm of chromosome 22 and one case with double subtelomeric
aberration consisting of a 12p deletion associated with 22q duplication
. Conclusion: MLPA screening is a fast, sensitive and cost-effective
technique for screening idiopathic mentally retarded patients with normal
karyotype . Validation by another cytogenetic or molecular method
is still needed for use in routine diagnostics .
P02.016
Array-cGH analysis in 48 patients with complex syndromic
phenotypes
E. F. Belligni1 , J. Messa2 , A. Vetro2 , C. Migliaccio1 , N. Chiesa1 , C. Molinatto1 , G.
A. Delmonaco1 , G. B. Ferrero1 , O. Zuffardi2 , M. Cirillo Silengo1 ;
1 2 Department of Paediatrics, Torino, Italy, Department of Genetics - University
of Pavia, Pavia, Italy.
Array comparative genomic hybridization (array-CGH) detects DNA
copy number variations, allowing to identify genetic imbalances in human
genetic disorders . We present the results of array-CGH analysis
in 48 children affected by mental retardation, congenital malformations,
and dysmorphic features . Standard karyotype was normal in all cases
but 3, array-CGH analysis detected a chromosomal imbalance in 19
patients: 7 deletions, 3 duplication, 1 tetrasomy, 2 double deletion, 1
double duplication and 5 more complex chromosomal rearrangements .
In a patient affected by a complex PEHO-like syndrome, characterized
by severe developmental delay, severe seizures, hyporegenerative
anemia, hypoalbuminemia and specific facial dysmorphisms, a de
novo duplication of 22q11.23 has been identified, allowing to define a
putative critical region for this complex developmental disorder . The
analysis confirmed the clinical diagnosis of five genomic syndromes
(Smith-Magenis, del1p36 .33, del9q34 .3, X-linked ichthyosis, Pallister-
Killian), and in 3 patients it identified a complex chromosomal rearrangement
previously described as a simple chromosomal anomaly
by standard karyotype . Rouling out the four cases in which the chro-