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

Clinical genetics
great importance prior pregnancy.
From 2001-2006 we performed a total of 1523 genetic counselings.
Results were as follows:
- 679 couples (44.5%) came for genetic counseling because of involvement
with a genetic disease and 844 couples (55.5%) came without
any genetic problem and only for assurance. Consangious marriages
905 cases (59.4%) was more common than unconsangious marriages.
Requesting for genetic counseling was: 678 couples (44.5%) prepregnancy,
588 couples (38.6%) prior marriage and 257 couples (16.9%)
during pregnancy. The most genetic disorders were:
Hemoglobinopathies: 307 cases (45.2% includes β- thalassemia,αthalassemia,sickle
cell anemia and other hemoglobinopathies)
Mental Retardation: 228 cases (33.9%)
Genetic syndromes: 40 cases (5.9% like apert,Turner,Ehlers-Danlos,…)
Recurrent abortion: 29 cases (4.2%)
Physical disabilithies: 29 cases (4.2%)
Deafness: 17 cases (2.5%)
Infertility: 12 cases (1,7%)
Neural tube defects: 8 cases (1.2%)
Blindness: 4 cases (0.5%)
Primary amenorrhea: 4 cases (0.5%)
The main conclusion is importance of genetic counseling prior marriage
and pregnancy because of high frequency of autosomal recessive
diseases due to consangious marriages in Iran.
P0125. Incomplete penetrance of G61E and R390H mutations in
CYP1B1 among Iranian Primary Congenital Glaucoma patients
F. Suri 1,2 , H. Amini Saroei 3 , S. Yazdani 4 , M. Pakravan 4 , N. Nilforooshan 5 , B.
Bayat 1 , E. Elahi 1,2,6 ;
1 National Institute for Genetic Engineering and Biotechnology, Tehran, Islamic
Republic of Iran, 2 Department of Biological Sciences, University of Tehran,
Tehran, Islamic Republic of Iran, 3 Farabi Eye Research Center, Department of
Ophthalmology, Tehran University of Medical Sciences, Tehran, Islamic Republic
of Iran, 4 Ophthalmic Research Center, Shaheed Beheshti University of Medical
Sciences, Tehran, Islamic Republic of Iran, 5 Department of Ophthalmology,
Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Islamic
Republic of Iran, 6 Bioinformatics Center, Institute of Biochemistry and Biophysics,
University of Tehran, 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 is cause of disease in approximately
70% of Iranian PCG patients and that the common mutations
in the population are G61E, R368H, R390H, and R469W. We have
now done a mutation screen in apparently unaffected family members
of pedigrees whose proband carried the G61E or R390H mutations.
Two apparently unaffected individuals carried G61E in the homozygous
state and one carried the R390H mutation in the homozygous
state. This indicates incomplete penetrance for these two mutaitons.
Incomplete penetrance for R390H has not been previously reported.
Incomplete penetrance has implications for role of the CYP1B1 gene
in pathogenesis and for diagnosis.
P0126. Screening for GCK and HNF1α mutations in Polish
women with gestational diabetes.
D. Januszkiewicz 1,2 , M. Zurawek 3 , E. Wender-Ozegowska 1 , J. Nowak 3 ;
1 Academy of Medical Sciences, Poznan, Poland, 2 Institute of Human Genetics,
Poznan, Poland, 3 Institute of Human Genetics Polish Academy of Sciences,
Poznan, Poland.
Mutations in the glucokinase (GCK) and hepatocyte nuclear factor 1α
(HNF1α) gene cause maturity-onset diabetes of the young (MODY)
type 2 and 3, respectively. The aim of the study was to examine the
prevalence of mutations in GCK and HNF 1α genes, in Polish women
with gestational diabetes mellitus (GDM). SSCP analysis and/or direct
sequencing of the coding regions of GCK and HNF 1α gene were done
in 119 Caucasian gestational diabetic subjects, fulfilling tree from the
following criteria: age G, IVS4+26C>A. All mutations were absent
from 210 control subjects (P< 0.05). In families carrying GCK mutations
the genotype- phenotype correlations were analyzed. In HNF1α
gene we identified 11 polymorphisms and 1 rare variant sequence
IVS5-27C>T. Our results indicated, that the frequency of mutations in
GCK in Polish population of gestational diabetes patients is not high.
P0127. Gomez-Lopez-Hernandez-Syndrome in a 6-yaers old boy
with behavior problems but normal intelligence
M. Hempel 1,2 , A. Pfeufer 1,2 , A. Weitensteiner 3 , P. Freisinger 3 , T. Meitinger 1,2 ;
1 Institute of Human Genetics, TU Munich, Munich, Germany, 2 GSF National
Research Center, Neuherberg, Germany, 3 Department of Pediatrics, TU Munich,
Munich, Germany.
We are reporting a boy who is the first child of healthy parents, born
in time after an uneventfull pregnancy with normal birth weight, lentgh
and head circumference. In the first year of his life feeding problems
occurred, failure to thrive, hypotonia and strabismus were noted. Motor
development was delayed. The boy started to walk at 18 month
and ataxia was diagnosed. The parents observed a sleep disturbance
beginning in the first weeks after birth. During the day the boy exhibited
hyperactive and aggressive behavior, as well as attention deficits. An
intelligence test revealed a normal IQ of 118. MRI of the brain at the
age of 6 years showed fusion of cerebellar hemispheres and agenesis
of the cerebellar vermis, the typical features of rhompencephalosynapsis.
No further abnormalities were found. An examination at the age of
6 years showed a long face with a high forehead, mid-face hypoplasia,
deeply set eyes, telecanthus, epicanthus inversus, broad nasal bridge,
pointed chin, deeply set posterior rotated ears and bitemporal alopecia
areata. Syndactyly of the toes II/III on both feet was present. Alopecia
and rhombencephalosynapsis together with trigeminal anesthesia are
the major symptoms of Gomez-Lopez-Hernandez-Syndrome, a very
rare sporadic syndrome. Since the first report in 1979 ten cases of
Gomez-Lopez-Hernandez-Syndrome have been reported. Additional
symptomes frequently described in Gomez-Lopez-Hernandez-Syndrome
are facial dysmorphism and craniosynostisis/asymmetric skull.
While the intellectual impairment is common in this syndrome our patient
showed normal intelligence. Difficulties in behaviour may be due
to the cerebellar abnormalities.
P0128. Gorlin syndrome in seven patients
E. Tunçbilek, G. E. Utine, F. Taşar, Y. Alanay, C. Tümer, H. Çetin, M. Saysel, S.
Balcı, D. Aktaş, K. Boduroğlu, M. Alikaşifoğlu;
Hacettepe University, Ankara, Turkey.
Gorlin syndrome is an autosomal dominant disorder characterized
by cutaneous basal cell carcinomas, odontogenic keratocysts and
skeletal anomalies. The prevalence is estimated from 1:57000 to
1:164000. Seven patients with Gorlin syndrome are presented. First
patient presented with macrocephaly, thick and prominent eyebrows,
a flat maxillary region, prognathism with mandibular hypertrophy and
cystic mandibular lesions, multiple hyperpigmented lesions and hypogonadotropic
hypogonadism. Triventricular widening and aqueductal
narrowing were detected. Chromosome analysis revealed 46,XX/
46,X,t(X;11)(q24;q13). The second patient had palmar pits, maxillary
hypoplasia and prognathism, odontogenic keratocysts and pigmentary
skin abnormalities. Third patient had mandibular and maxillary
odontogenic keratocysts and at two years of age hydrocephaly was
diagnosed. He had macrocephaly, thick eyebrows, synophrys, downslanting
and wide palpebral fissures, generalised skin hyperpigmentation
and mild prognathism. Other two patients were a mother and
her daughter. The mother had maxillary and mandibular cysts, basal
cell carcinoma and scoliosis. Her father died of skin cancer. Her 5year-old
daughter had macrocephaly, coarse facies, partial agenesis
of corpus callosum and café-au-lait spot. Last two patients were two
brothers, both having gingival hyperplasia and odontogenic cysts. The
elder brother had millimetric calcifications on the anterior part of falx
cerebri, as demonstrated by cranial tomography. Both had atrophic
depigmented skin lesions and the elder brother had palmar pits. The
younger brother was unable to read, he had diffuse calvarial thickening
in cranial CT and his chromosome analysis was 47,XXY. Gorlin