2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
P02.076
study of D2 dopamine receptor (DRD2) gene expression, in
morphine-sensitized mice in the absence and presence of Licl
H. Mehregan 1 , M. Sadeghizadeh 1 , M. Zarrindast 2 , K. Azadmanesh 3 , A. Jahanshahi
4 ;
1 Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University,
tehran, Islamic Republic of Iran, 2 Department of Pharmacology, School of
Medicine, Tehran Uuniversity of Medical science, tehran, Islamic Republic of
Iran, 3 Hepatitis and AIDS Dept., Pasteur Institute of Iran, tehran, Islamic Republic
of Iran, 4 Department of Physiology, Faculty of Medicine, Tarbiat Modares
University, tehran, Islamic Republic of Iran.
One of the consequences of repeated morphine administration is sensitization
in which the intermittent exposure to a fixed dose of drug
results in a greatly enhanced behavioral response to further morphine
administration. The neurotransmitter, dopamine, is involved in several
functions of the brain. Of all the five DRDs, D2 receptor has maximal
affinity for dopamine; there is a growing evidence for the role of D2
receptor in different aspects of addiction
In this study, the expression level of dopamine D2 long (D2L) and D2
short (D2S) isoforms of D2 receptor in morphine-sensitized mice were
investigated in the absence and presence of LiCl (5 and 10 mg/kg).
Morphine sensitization was induced by once daily injection of morphine
(30 mg/kg) for 3 days, followed by 5 days wash-out. Using relative
Real-Time PCR, D2L and D2S expression were examined in the
brain regions including striatum, PFC and hippocampus. We found
that morphine treatment leads to a significant increase in D2S level in
the striatum and PFC but has no effect on D2L level in the examined
regions. While administration of LiCl 5mg/kg along with morphine does
not alter D2L and D2S isoforms, LiCl 10 mg/kg treatment results in a
markedly increase in D2S but not D2L expression level in the striatum
and PFC of sensitized mice. The result indicates that morphine sensitization
leads to an increase in presynaptic D2S receptor expression
level and is affected by lithium in a dose-dependent manner with low
dose to inhibit and higher dose to enhance the effect.
P02.077
mucopolysaccharidosis type iH - A case report
E. Kiss 1 , C. Duicu 1 , C. Banescu 2 , V. Bodescu 1 , I. Pascanu 2 , K. Csep 2 ;
1 Pediatric Department, Univeristy of Medicine and Pharmacy, Tg Mures, Romania,
2 Genetic Department, Univeristy of Medicine and Pharmacy, Tg Mures,
Romania.
Mucopolysaccharidosis Type IH (OMIM #607014) or Hurler Syndrome
is the most common disorder of the group of seven mucopolysaccharide
storage disorders. MPS IH is inherited in an autosomal recessive
manner. The estimated incidence is approximately 1:100,000
newborns. MPS IH is caused by mutation in the gene encoding α-
L-iduronidase. Deficiency of α-L-iduronidase conduct to progressive
accumulation of undegraded glycosmaminoglycans in all bodily tissues.
Our proband is a 5 years old male, the only child of an unrelated
couple who was addmited in our clinic for severe respiratory distress.
A comprehensive medical evaluation was made: prenatal and birth history,
physical, neurologic and genetic examinations, biologic and imagistic
evaluations (cardiac and abdominal ultrasonography, chest, hand
and skull X-ray). By clinical examination we noticed: mental and motor
development retardation, gibbus deformity, claw hand deformity, short
stature, coarse facies, large head, proeminent forehead, hypertrichosis,
corneal clouding, hepatosplenomegaly, abdominal enlargement,
inguinal hernia, wheezing. His past medical history revealed recurrent
ear and respiratory infections. Positive diagnosis was based on association
of clinical signs, imagistic evaluation and enzyme deficiency
testing- which demonstrated absent α-L-iduronidase activity in plasma.
Unfortunately his parents refused enzyme replacement therapy (Aldurazyme®)
in spite of his poor condition, knowing it’s evolution and
prognosis. Proper genetic counselling was offered. Prognosis of our
case is linked to the respiratory and cardiovascular complications. In
conclusion,we present a case of MPS IH in order to illustrate this rare
genetic disorder but also to discuss the positive diagnosis, the management
and the genetic counseling.
P02.078
severe congenital cyphoscoliosis associated with multiple
congenital anomalies in an adolescent boy
G. Doros1 , M. Gafencu1 , A. Popoiu1 , B. Zoica1 , M. Popoiu1 , M. Marusteri2 , G.
Miclaus2 ;
1 2 University of Medicine &Pharmacy, Timisoara, Romania, Neuromed Clinic,
Timisoara, Romania.
Aim: To present a 17 yo boy, with multiple malformations admitted for
an accurate treatment.
Matherial and methods: The patient was diagnosed at birth with congenital
cyphoscoliosis, Fallot tetralogy, pulmonary atresia, single kidney
and sindactily of the left hand. His teeths, developed anarchic. At
the age of 7 was operated for a Blalock Taussing shunt. He has 19.5
Kg, 132 cm, generalized muscular hypotonia and hypothrophia, cyanosis,
congenital severe thoraco-lumbar sinistro-concave cyphoscoliosis,
secondary sterno-condral asymmetry, apex located in left axillae,
gr. III/6 continous thoracic murmur, and is extremely clever. Laboratory
tests revealed poliglobuly and slightly elevated liver enzymes. He performed
a lot of paraclinic investigations.
Results: The cardiac examination mentioned also: MAPCA, anomalies
of the aortic arch and gr. II aortic insuficiency. Neurologicaly was found
generalized muscular dystrophy. Abdominal ultrasound developed two
hepatric tumors, one left kidney and multiple vascular anomalies. Surgical
exam described a Marfan fenotipe. Thorax Angio CT confirmed
aortic arch anomalies, Lusoria artery and multiple arterial connections
to the lungs. Abdominal MRI developed three hepatic tumors, one hepatic
nodular fibrosis and two small hepatic hemangioma. The patient
is in chronic heart failure treatment with Digoxin, antiagregant therapy
and vitamins for the liver. He is suspected of hemangioendothelioma .
Conclusions: Because of his poor clinical condition, severe column cyphoscoliosis
and multiple associated malformations, the patient was
temporized for the final surgical cardiac repair. His column needs surgical
stabilization. The hepatic tumors needs fine needle biopsy. We
have to decide the priorities in treatment for a psedo-normal life.
P02.079
mURcs Association With situs inversus totalis: A case Report
U. Çetinçelik1 , C. Sayar2 ;
1 2 Sisli Etfal Training & Research Hospital, İstanbul, Turkey, Zeynep Kamil Gynecologic
and Pediatric Training and Research Hospital, İstanbul, Turkey.
MURCS association is a rare, developmental disorder which involves
the Mullarian duct, the kidneys and the cervicothoracic spine. It is a
sporadic disorder with unknown etiology. The prevalence is 1/50000
female. Occasionally, it may be accompanied by abnormalities involving
various other organs or systems. A 24 year old woman came to
our clinic suffering from primary amenohrrea, then she was diagnosed
MURCS association.
Röntgenograms showed thoracolumbar vertebral defects-scoliosis
and abdominal MRI revealed pelvic renal ectopy, the absence of the
uterus and also the upper part (2/3) of the vagina. MRI revealed also
presented situs inversus totalis which is a very rare anatomic condition.
Her karyotype was normal 46,XX. This is the first report of situs
inversus totalis in a case of MURCS association.
P02.080
two cases of myhre syndrome with retinopathy: further
delineation of the phenotype
S. Whalen1 , A. Afenjar1 , D. Doummar2 , N. Dorison2 , S. Chantot-Bastaraud3 , B.
Keren1 , D. Héron1 ;
1Dpt de Génétique Cytogénétique et Embryologie, Hôpital Pitié Salpêtrière,
Paris, France, 2Service de Neuropédiatrie, Hôpital Trousseau, Paris, France,
3Service de Génétique et d’Embryologie médicales, Hôpital Trousseau, Paris,
France.
Myhre syndrome is characterised by facial dysmorphism, short stature,
joint limitations, brachydactyly, muscle hypertrophy, hearing loss
and mental retardation. Specific radiological findings include thickened
calvarium, hypoplastic iliac wings, broad ribs, and abnormal vertebrae.
No genetic basis has been identified.
We report two unrelated patients with Myhre syndrome, who both had
retinopathy, undescribed up to date.
Patient 1, a 13 year old male, presented with typical dysmorphism, language
delay, learning difficulties, obesity, precocious puberty, brachydactyly,
athletic build, joint limitations, and thick skin. Height was nor-