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

Clinical genetics
which has not been reported previously. This is SRNS patient of 2
years old, with manifestation of disease at the age of 1 month with
rapid progression to the End Stage Renal Disease. In this case we can
propose digenic type of inheritance. Perhaps, the most our patients`
disease is caused by mutation in over genes coding proteins being involved
in the structure and the function of the kidney filtration barrier.
This work was partly supported by Russian President`s grant NSh-
5736.2006.7.
P0207. Mutation screening of melanocortin 4 receptor (MC4R) in
a Norwegian cohort of obese patients reveals a low prevalence
and four novel mutations.
T. Wangensteen 1,2 , M. Pollestad 3 , M. Mattingsdal 4 , S. Tonstad 5 , D. Undlien 2,1 ,
L. Retterstøl 1 ;
1 Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway,
2 Institute of Medical Genetics, University of Oslo, Oslo, Norway, 3 Department of
Pediatrics, Ullevål University Hospital, Oslo, Norway, 4 Department of Medical
Informatics, Rikshospitalet-Radiumhospitalet, Oslo, Norway, 5 Department of
Preventive Cardiology, Ullevål University Hospital, Oslo, Norway.
Backgound: Heterozygous mutations in the melanocortin 4 receptor
(MC4R) gene are the most frequent monogenic cause of obesity. Previous
studies of such mutations have given prevalences varying from
0.5 up to 5.8%.
Materials and methods: We sequenced the coding region of the MC4R
gene in 703 obese Norwegian subjects. The patients were recruited
from an ongoing study at Ullevål University Hospital. Adults with
BMI>35 kg/m² and children whose bodyweight was above the 97.5
th percentile for height were asked to participate. All novel mutations
were analyzed by a bioinformatic approach and family studies.
Results: 6 mutations were identified, two previously described and four
new ones. A total of three different mutations were found among the
459 adults, giving a prevalence of 0.65%. Four patients with mutations
were found among 244 children corresponding to a prevalence of
1.6%. Several known polymorphisms were also identified.
All mutations identified in the pediatric group were in second-generation
immigrants, who made up more than half of this group. The same
novel mutation was found in two siblings whose parents are first cousins.
Both children are homozygous for a 3-bp-deletion in the MC4Rgene.
The other patients were all heterozygous for their mutation.
Two previously described mutations, p.Tyr35X and p.Thr150Ile were
found in female patients with adult onset obesity.
Conclusions: Mutations in the MC4R gene are not a common cause of
obesity in Norway. Four of the six mutations identified have not been
described previously.
P0208. Oculo-Facio-Cardio-Dental (OFCD) syndrome: Somatic
mosaicism of a large BCOR gene deletion in 2 monozygotic
twins and three novel mutations
S. Whalen 1 , S. Manouvrier 2 , O. Boute 2 , F. Fellmann 3 , F. Dastot-Le Moal 1 , P. Bitoun
4 , M. Cordier 5 , I. Bailleul-Forrestier 6 , M. Goossens 1 , A. Verloes 6 , I. Giurgea 1 ;
1 Dpt de génétique et INSERM U841, Hôpital Henri Mondor, Créteil, France,
2 Service de génétique clinique, Centre Hospitalier Régional Universitaire de
Lille, Lille, France, 3 Service de génétique médicale, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland, 4 Dpt de génétique, Hôpital Jean Verdier,
Bondy, France, 5 Dpt de génétique médicale, Hôpital Edouard Herriot, Lyon,
France, 6 Dpt de génétique médicale, Hôpital Robert Debré, Paris, France.
Oculo-Facio-Cardio-Dental (OFCD) syndrome is a rare disorder associating
congenital cataract, microphthalmia, characteristic dysmorphia,
congenital heart defects, oligodontia, and radiculomegaly.
OFCD syndrome results from mutations in the BCOR gene, located
on Xp11.4, encoding a key transcriptional regulator during early embryogenesis.
X-linked dominant inheritance is suggested, although a
singular BCOR missense mutation, whose relevance remains controversial,
was described in a male presenting with Lenz microphtalmia
syndrome (microphtalmia, mental retardation, and multiple congenital
abnormalities).
To further delineate the clinical spectrum of these disorders, we studied
seven females with OFCD syndrome and four males with Lenz
microphtalmia, from six unrelated families. BCOR mutations were
screened by direct sequencing, QM-PSF, and deletions were confirmed
by FISH analysis.
Somatic mosaicism for a large deletion of BCOR (45 % in peripheral
leukocytes) was identified in two monozygotic twins presenting with
typical OFCD syndrome. One twin transmitted this large deletion homogeneously
to her daughter. In addition, three novel mutations were
identified in three unrelated females: two frameshift (p.Pro288ArgfsX90
and p.Pro190ProfsX26), and one nonsense (p.Arg1480X) mutation.
No mutation of BCOR was found in the male patients with Lenz microphtalmia.
In conclusion, we report four novel BCOR mutations in females with
OFCD syndrome. These results broaden the clinical spectrum of OFCD
syndrome, as three patients did not present heart defects, and one patient
had mild mental retardation, thus suggesting that the condition is
underdiagnosed. The first description of somatic mosaicism in OFCD
syndrome is of particular relevance to genetic counselling.
P0209. A natural history of a six years-old girl with Ohdo
syndrome
R. Posmyk, A. T. Midro;
Department of Clinical Genetics, Medical Academy, Bialystok, Poland.
Ohdo blepharophimosis syndrome (OBS) (249620 #OMIM) is a rare
genetic entity characterized by blepharophimosis, blepharoptosis,
dental hypoplasia, heart disease, short stature and intellectual disability.
The phenotypic variability in OBS has been reported . We present
a natural history of a girl observed during six years from the birth. OBS
has been recognized on the basis of following features: short stature,
blepharophimosis, ptosis of eyelids, epicanthic folds, microphtalmia,
flat, wide nasal bridge, narrow mouth fissure, long philtrum, thin upper
lip, high palate, hypoplastic teeth, dysplastic, low-set ears, joint laxity,
scoliosis, sacral dimple, congenital heart anomaly (pulmonary stenosis,
VSD, PDA, PFO), severe hypotonia and distinct developmental
profile. Morphological phenotype has been described according to
the catalogue elaborated by Stengel Rutkowski et al. and evolution of
some traits has been found. Interestingly, some features as: a very soft
skin, curly, fragile hair , a lack of nose cartilage, small maxilla and, a
radiological abnormalities in knees resembling Blout disease were not
previously described in relation to this syndrome.
We suggest that a better knowledge of the clinical and anthropological
spectrum of OBS can be helpful for setting a diagnosis as molecular
basis of this disorder remains still unknown.
P0210. Ophthalmic status of patients with Goldenhar syndrome
O. K. Yanvareva, E. Drozdova, M. O. Mkheidze;
Medical Academy for postgraduate studying, St.Petersburg, Russian Federation.
Aim of the work: investigation of ophthalmic status of patients with
Goldenhar (facio-auriculo-vertebral) syndrome.
Material and methods. There were 5 patients (10 eyes, 3 males and
2 females aged from 6 to 27 yr) with Goldenhar syndrome under our
observation. Routine basic ophthalmic investigation was performed for
all patients.
Results. Ophthalmic status of all patients included sclera-corneal lipodermoid
(6eyes) followed by reduced vision and demanding partial
fibered keratoplasty (1 case) and optic correction picking up of all the
patients because of astigmatism (5 patients). Two clients had petite
lipodermoid of sclera without surgical correction. One client had inborn
anomaly in the form of the upper lid coloboma removed with surgical
intervention. All clients were operated on in early childhood apropos of
a cleft lip and a palate. A 10 year-old boy had atresia of the auditory
passage and the malformed ear followed by unilateral inborn hearing
disorder. Mental development of all clients was intact. Our clients’
relatives denied congenital and inherited pathology. Correction of refractional
amblyopia with spectacles resulted in stable and high visual
function. Development of xerotic cornea of the eye with the upper lid
coloboma was prevented.
Conclusion. To make diagnosis at proper time and correct face, eye
and ear dysplastic features using surgical intervention by ophthalmologists,
orthodontists and specialists of aesthetic surgery are sine qua
non for successful life and disease prognosis.
P0211. Orofacial clefts with associated anomalies in Lithuania
E. Zarakauskaitė 1 , A. Matulevičienė 2 , A. Utkus 1,2 , L. Linkevičienė 3 , V.
Kučinskas 1,2 ;
1 Department of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania,
2 Centre for Medical Genetics at Vilnius University Hospital Santariskiu
Klinikos, Vilnius, Lithuania, 3 Institute of Odontology, Vilnius University, Vilnius,
1