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

Cytogenetics
to reports from Saudi Arabia and Kuwait but the frequency of abnormalities
varied with a mixture of +8, t(8;21) & t(15;17). Morphologically
our patients differed with M2 subtype as the commonest, whereas,
their reports showed M4 and M3 subtypes as most frequently occurring
subtype in their patient population respectively.
P0290. Screening of subtle copy number changes in Aicardi
Syndrome Patients with a high resolution X-chromosome array-
CGH
S. Yilmaz 1 , H. Fontaine 1 , K. Brochet 1 , M. Grégoire 1 , M. Devignes 2 , J. Schaff 1 , C.
Philippe 1 , C. Nemos 1 , J. McGregor 3 , P. Jonveaux 1 ;
1 University hospital of Nancy, Vandoeuvre les Nancy, France, 2 CNRS-UMR
7503, LORIA, Vandoeuvre les Nancy, France, 3 INSERM Unité 689, Paris,
France.
Aicardi syndrome is a very uncommon neurodevelopmental disorder
affecting almost exclusively females. Chief features include infantile
spasms, corpus callosal agenesis, and chorioretinal abnormalities.
Aicardi syndrome is a sporadic disorder and hypothesized to be caused
by heterozygous mutations in an X linked-gene but up to now without
any defined candidate region on the X chromosome. Array based comparative
genomic hybridisation has become the method of choice for
the detection of microdeletions and microduplications at high resolution.
In this study, for the first time, 18 Aicardi syndrome patients were
analyzed with a full-coverage X-chromosomal BAC arrays at a theoretical
resolution of 82 kb. Copy number changes were validated by real
time quantitation. No disease-associated aberrations were identified.
For such conditions as Aicardi syndrome, in which there are no familial
cases, additional patients should be studied in order to identify rare
cases with submicroscopic abnormalities, and to pursue a positional
candidate gene approach.
P0291. The role of chromosomal abnormalities in primary
amenorrhoea
B. O. Petrovic, A. Ljubic;
Institute for gynecology and obstetrics, Belgrade, Serbia.
Amenorrhoea is absence or cessation of menses. If menstruation does
not begin by the age of 16 years in the presence of female secondary
sexual maturation, or does not begin by 14 years in the absence
of secondary sexual maturation, the condition is classified as primary
amenorrhoea. This paper deals with investigation of how primary
amenorrhoea and chromosomal abnormalities are related. For the
period of last ten years we have analyzed 62 patients with primary
amenorrhoea. Karyotype from the peripheral blood lymphocytes and
G banding were performed according to standard protocols. Chromosomal
abnormalities were detected in 16 cases (25,8%). Male karyotype
(46,XY) was found in seven cases. In three cases monosomy X
(45,X) was found. In two cases isochromosome X (46,XiXq) was detected,
as well as a case of X chromosome trisomy (47,XXX). Mosaic
karyotypes 45,X/46,XiXq, 46,XX/47,XXY and 45,X/46,XX were found
in one case each. These findings suggest that a consistent number of
cases with primary amenorrhoea (about 25%) can be associated with
genetic anomalies.
P0292. Array-CGH analysis: new deletion syndromes and
atypical phenotype in old deletion syndromes
R. Caselli, F. Mari, F. T. Papa, M. A. Mencarelli, V. Uliana, F. Ariani, I. Meloni, I.
Longo, A. Renieri;
Medical Genetics, University of Siena, Siena, Italy.
A group of 28 unrelated MCA/MR patients with normal karyotype, selected
from those attending the Medical Genetics Unit of the University
of Siena has been analyzed by oligo array-CGH with an average
resolution of 75Kb (Agilent Human Genome CGH Microarray Kit 44B).
A new “de novo” deletion has been identified in 3 patients (table 1).
During the screening, we have also identified, 3 known deletions in
atypical patients, 1 duplication reciprocal of the deletion responsible
for Smith-Magenis and 2 polymorphisms (table 2).
In conclusion, in this highly selected population we identified pathogenic
segmental deletions/duplications in 7 out of 28 patients (about
25%). We compared the clinical features of patients with new deletions
with other rare cases described in the literature in order to define clinical
diagnostic criteria useful in the clinical practice. In particular, for the
6q25 deletion the emerging phenotype is characterized by short palpebral
fissures, smooth philtrum, thin upper lip, asymmetric dysplastic
protruding ears, heart septal defect, and slightly delayed psychomotor
development. These characteristics should be taken into account in
order to identify other patients.
P. Clinical features
1
2
3
Table 1. New deletions
4y2m girl with postnatal growth retardation,
microcephaly, ptosis, down-slanting palpebral
fissures, long eyelashes and micrognathia.
Halluces are long, broad and medially deviated,
while the other toes are laterally deviated and
remarkably short with hypoplastic phalanges.
She shows developmental delay, seizures, lack
of eye contact, hand stereotypies and sleep
disturbances with breath holding
13y8m boy with severe mental retardation,
absence of speech, sleep disturbances, behavioural
problems. He presents macrocephaly, high
forehead, thick and coarse hair, thick eyebrows,
synophris, increased inner and outer canthal distance,
bifid nasal tip, high palate, micrognathia,
dysmorphic, right ear, bilateral sandal gap and
long and tapering fingers.
7y6m female with neurodevelopmental delay,
postnatal short stature and atrial septal defect.
Patent ductus arteriosus and tricuspid insufficiency
were also noted at birth. Medial flare
eyebrows, dysmorphic helix of the right ear,
cupshaped left ear, anteverted nares, long and
smooth philtrum, thin upper lip, high vaulted
palate are noted.
Clinical features
Case 1. Hypotonia, seizures, ataxia, sleep
disturbances, gastroesophageal reflux,
dolichocolon, hypospadia, monolateral
inguinal hernia, bilateral 2-3 syndactyly
of toes.
Case 2. Bilateral corneal leukoma, iris and
retinal coloboma, cleft lip and palate, VSD,
postaxial polydactyly of hands and feet.
Case 3. MURCS association , short stature,
delayed bone age, long faces, tubular
nose with bulbous tip, high palate and
nasal speech, small and low-set ears, left
carotid artery hypoplasia.
Case 4. Psycomotor delay, obesity, round
facies, macroglossia and macrostomia,
prognathism, synophris, thick eyebrows,
strabism, depressed nasal bridge, bulbous
nasal tip, small feet.
Case 5. Neonatal hypotonia, mild mental
retardation, visuo-spatial deficit, sociable
attitude, hoarse voice, strabismus, dysmorphic
features such as telecantus, epicantus,
down-slanting palpebral fessures,
medial flared eyebrows.
Case 6. Truncal obesity, tall stature, hypoacusya,
hypothyroidism.
Chr.
Deletion size
Breakpoints
2q24.3-31.1
10.4 Mb
165.580-175.871 Mb
2q31.2-32.3
13 Mb
180.13-192.88 Mb
6q24.3-25.1
2,6 Mb
148.785-151.289 Mb
Table 2. Other results.
Chr.
Position
(approximate
size)
15q11-13.1
165.8-175.8
(5 Mb)
22q11.21
17.2-19.7
2.5 Mb
22q11.21
17.2-19.7
2.5 Mb.
17p11.2
16.5-20.1
3.6 Mb
17p11.2
16.5-20.1
3.6 Mb
Xq25.1
124.7-127.5
2.8 Mb
Case 7. Mental retardation, obesity, thick
2q37.3-qter
lips, large prominent teeth, tapering fingers,
242.4-ter
wave shaped eyelids.
0.5 Mb
Type of rearrangement
deletion
deletion
deletion
deletion
duplication
deletion
deletion
Reference
Pescucci et
al, Eur J Med
Genet, 2007,
50:21-32
Mencarelli et al,
in press, Am J
Med Genet
Caselli et al,
in press, Eur J
Med Genet
Conclusions
Known deletion
in atypical patient
Reciprocal of the
Smith-Magenis
syndrome deletion
Polymorphism
P0293. Array-CGH screening in 100 patients with mental
retardation
E. Landais 1 , A. Schneider 1 , N. Bednarek 2 , P. Sabouraud 2 , J. Motte 2 , J.
Couchot 3 , M. Khoury 4 , R. Klink 4 , E. Lagonotte 1 , C. Leroy 1 , M. Mozelle 1 , D. Gaillard
1 , M. Doco-Fenzy 1 ;
1 Service de Génétique, CHU Reims, UFR de Médecine, Reims, France, 2 Service
de Pédiatrie, American Memorial Hospital, Reims, France, 3 Service de
Pédiatrie, CHG, Charleville, France, 4 Service de Pédiatrie, CHG, Laon, France.
Mental retardation (MR) is a major problem affecting 3% of the population.
Chromosome imbalances larger than 5 Megabases are detected
by 550 band resolution R or G band karyotype. The Array-CGH is able
to detect interstitial smaller deletions or duplications.
We report on the results obtained by molecular karyotyping with 1Mb
BAC and PAC array-CGH screening in a population of 100 patients
affected by MR with or without multiple congenital anomaly (MCA). For