2008 Barcelona - European Society of Human Genetics

Clinical genetics
objectives of our study were to characterize the neuropsychological
aspects of patients with MFDH, to correlate them with neuroimaging
findings and to investigate the 22q11.2 deletion in these patients. Neuropsychological
evaluation was performed using the Luria Nebraska
Battery and WISC for children and WAIS for adults; the 22q11 .2 deletion
was investigated by FISH . Heterogeneous results on neuropsychological
evaluation involved difficulties cognitive domains such as
picture arrangement, expressive language, comprehension, arithmetic,
digit span and motors ability . These abnormalities are similar, in
part, to those reported in deletion of 22q11 .2 region, which was not
detected in all cases . In conclusion, we found a relationship between
neuropsychological and radiological CNS alterations in MFDH . As the
22q11 .2 region is recognized as critical for embryonary development
of midline, in view of the clinical-genetic heterogeneity and the specified
of the probe used, the involvement of 22q11.2 region in the etiology
of MFDH needs to be further investigated .
P01.289
Associated malformations in patients with gastroschisis and
omphalocele
C. Stoll, Y. Alembik, B. Dott, M. Roth;
Genetique medicale, Strasbourg, France.
The etiology of gastroschisis and omphalocele (exomphalos) is unclear
and their pathogenesis is controversial . However, the reported types
and frequency of malformations associated with omphalocele and gastroschisis
vary between studies . The purpose of this investigation was
to assess, in a geographically defined population, the prevalences at
birth of associated malformations in patients with omphalocele and gastroschisis
which were ascertained between 1979 and 2003 in 334,262
consecutive births . Of the 86 patients with omphalocele, 64 (74 .4%)
had associated malformations including chromosomal abnormalities
(25 cases,29 .0%); non chromosomal recognized syndromes including
Beckwith-Wiedemann, Goltz, Marshall-Smith, Meckel-Gruber, Oto-palato-digital
type II, CHARGE, and fetal valproate; sequences, including
ectopia cordis, body stalk anomaly, exstrophy of bladder, exstrophy
of cloaca, and OEIS; malformation complex including Pentalogy of
Cantrell, and patients with non syndromic multiple congenital anomalies
(MCA) (26 cases, 30 .2%) . Malformations of the musculoskeletal
system (23 .5%), the urogenital system (20 .4%), the cardiovascular
system(15 .1%), and the central nervous system(9 .1%), were the most
common other congenital anomalies occurring in patients with omphalocele
and MCA . For gastroschisis, the total prevalence was 1 .79 per
10,000. However, there was a significant increase over the study period
in the total prevalence. The maternal age-specific prevalence was
highest in the 15-19 year age group . Of the 60 patients with gastroschisis,
10 (16 .6%) had associated malformations including one skeletal
dysplasia, one amyoplasia congenita, and 7 non syndromic MCA . In
conclusion the overall prevalences of malformations associated with
omphalocele and gastroschisis are quite different and emphasizes the
need for a thorough screening of cases for other malformations .
P01.290
Discordance of primary congenital glaucoma in monozygotic
twins
F. Suri 1,2 , S. Paylakhi 3 , S. Yazdani 4 , S. Zeinali 5 , M. Sajedifar 6 , S. Zargar 1 , E.
Elahi 1,2 ;
1 School of Biology, University College of Science, University of Tehran, Tehran,
Islamic Republic of Iran, 2 National Institute of Genetic Engineering and Biotechnology,
Tehran, Islamic Republic of Iran, 3 School of Biology, University College
of Science, University of Tarbiat Modarres, Tehran, Islamic Republic of Iran,
4 Ophthalmic Research Center, Shaheed Beheshti University of Medical Sciences,
Tehran, Islamic Republic of Iran, 5 Biotechnology Department, Pastuer
Institute of Iran, Tehran, Islamic Republic of Iran, 6 Kausar Biotechnology Company,
Tehran, Islamic Republic of Iran.
Glaucoma is a heterogeneous group of optic neuropathies characterized
by degeneration of the optic nerve, usually associated with elevated
intraocular pressure . It is the cause of 15% of blindness worldwide .
Primary Congenital Glaucoma (PCG), one of the three major forms of
the disease, becomes apparent at birth or before the age of three and
is a major cause of childhood blindness . Mutations in both alleles of
the cytochrome P4501B1 (CYP1B1) gene, which is the only gene thus
far linked to PCG, result in the disease phenotype . It has been recently
shown that mutations in this gene are cause of disease in approxi-
mately 70% of Iranian PCG patients and that the common mutations in
the population are G61E, R368H, R390H, and R469W .
We report here the observation of highly variable expression of primary
congenital glaucoma in two individuals who are identical twins .
Both carried the G61E mutation in the homozygous sate . The identical
twin status of the individuals was confirmed using several microsatellite
markers .
P01.291
Cloning & Expression of Human rFVII in Insect Cells
N. Masroori, M. Habibi Roudkenar PhD;
Iranian Blood Transfusion Organization, Tehran, Islamic Republic of Iran.
Hemophilia is the one of the most prevalent genetic disorders . It is
inherited as sex-linked pattern . Obtaining factor from plasma or by recombinant
technology, in high dose is one of the major challenges
for treatment of Hemophilia . However 25% of these patients naturally
raised antibody against factor VIII . Viral contamination and availability
in very low dose is another challenge to obtain factor VIII from plasma .
Administration of Recombinant factor VII for patients who raised antibody
against FVIII can be one of the solution for mention problem .
Isolation, cloning and expression of recombinant FVII by Gateway
technology was the aim of this study . Factor VII gene was isolated from
HepG 2 cell line and cloned to TOPO vector by TOPO cloning method .
The construct was ligated to Baculovirus destination vector by LR recombination
using getaway technology and the recombinant virus was
transfected to, insect cell line, SF9 . Expression of recombinant FVII
was detected by SDS-PAGE, ELISA and western blot analysis .
P01.292
A prenatally detected case of congenital hepatoblastoma
H. Ergin 1 , B. Yildirim 2 , E. Dagdeviren 1 , B. Yagci 3 , F. Ozen 4 , N. Sen Turk 5 , S. E.
Duzcan 5 ;
1 Department of Pediatrics, Pamukkale University Faculty of Medicine, Denizli,
Turkey, 2 Department of Obstetrics and Gynecology, Pamukkale University
Faculty of Medicine, Denizli, Turkey, 3 Department of Radiology, Pamukkale
University Faculty of Medicine, Denizli, Turkey, 4 Department of Pediatrics, Ege
Hospital, Denizli, Turkey, 5 Department of Pathology, Pamukkale University
Faculty of Medicine, Denizli, Turkey.
Hepatoblastoma is a rare tumor of childhood . The incidence of hepatoblastoma
in the first year of life is about one in a million. The mean
time of its onset is 14 to 24 months . Forty-two congenital hepatoblastoma
cases were reported so far . Among 42 congenital hepatoblastoma
patients, seven cases have been detected in the prenatal period
. Only one out of seven cases detected in the prenatal period has
been diagnosed as hepatoblastoma . The etiology of hepatoblastoma
is unknown . However, it has been shown to be associated with prematurity,
low birth weight, hepatitis B, familial adenomatous polyposis,
Beckwith-Wiedemann syndrome and hemihypertrophy . In this report,
we report a rare case of hepatoblastoma detected before birth and
confirmed by postmortem.
P01.293
Genotype-phenotype correlation in hereditary hemorrhagic
telangiectasia in patients with ACVRL mutations: is c.1112dupG
mutation a milder mutation?
S. Dupuis-Girod 1 , S. Giraud 1 , E. Decullier 1 , B. Gilbert-Dussardier 2 , M. Carette 3 ,
G. Plessis 4 , S. Riviere 5 , P. Magro 6 , G. Lesca 1 , P. Edery 1 , A. Calender 1 , H. Plauchu
1 ;
1 Hospices Civils de Lyon, LYON, France, 2 Hôpital Jean Bernard, POITIERS,
France, 3 Assistance Publique - hôpitaux de Paris, PARIS, France, 4 Hôpital Côte
de Nacre, CAEN, France, 5 Hôpital Saint Eloi, Montpellier, France, 6 Hôpital Bretonneau,
TOURS, France.
Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal
dominant disorder characterized by recurrent epistaxis, cutaneous
telangiectasia, and visceral arteriovenous malformations
(AVMs) that affecting lungs (PAVM), gastrointestinal tract (DAVM), liver
(HAVM), and brain (CAVM) and resulting from mutations in two major
genes: ENG (HHT1) or ACVRL1 (HHT2) .
Our objective was to determine the influence of c.1112dupG mutation
on clinical phenotype in HHT2 patients .
Methods: We retrospectively compared the frequency of clinical features
of HHT between a subgroup of patients with mutation c .1112dupG
(group A) and those with the other ACVRL1 mutations (group B), using
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