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

Clinical genetics
itar syndrome, which is a rare anomaly of pulmonary venous return to
the vena cave inferior.
Chromosome analysis on routine G-banded chromosomes was normal.
However, CGH showed a deletion on chromosome 10(p11.2p12.1).
Extended G-banding (900 band-level) and array CGH confirmed the
deletion, and breakpoints were suggested to be (p11.23p12.1).
Several deletions in the short arm of chromosome 10 have been published
in literature and in the ECARUCA chromosome database, but
to our knowledge these deletions are all larger than the deletion our
patient has. In addition, all patients described have a more severe phenotype
than our patient. Deletions in the short arm of chromosome
10, at or near 10p13, are associated with a DiGeorge syndrome-like
phenotype, DiGeorge 2 syndrome (DGS2). Yatsenko et.al (2004) reviewed
19 patients with deletion in 10p and congenital heart defects
(CHD) and found that atrial septum defect (ASD) is a common cardiac
anomaly associated with DGS2. Thus, the short arm of chromosome
10 may comprise one ore more critical regions for normal development
of the cardiopulmonary system.
P0024. Arterial tortuosity syndrome: clinical and molecular
findings in 12 newly identified families
B. L. Callewaert 1 , A. Willaert 1 , W. S. Kerstjens-Frederikse 2,3 , J. De Backer 1 ,
K. Devriendt 4 , B. Albrecht 5 , M. A. Ramos-Arroyo 6 , M. Doco-Fenzy 7 , R. C. M.
Hennekam 8,9 , R. E. Pyeritz 10 , G. Gillessen-Kaesbach 11 , E. L. Wakeling 12 , S. Nik-
Zainal 13 , C. Francannet 14 , P. Mauran 15 , C. Booth 16 , M. Barrow 17 , P. J. Coucke 1 ,
B. L. Loeys 1 , A. M. De Paepe 1 ;
1 Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium,
2 University Medical Center Groningen, Groningen, The Netherlands, 3 University
of Groningen, Groningen, The Netherlands, 4 Center for Human Genetics,
University of Leuven, Leuven, Belgium, 5 Institut für Humangenetik, Universitätsklinikum
Essen, Essen, Germany, 6 S. Genética Médica, Hospital Virgen
del Camino, Pamplona, Spain, 7 Service de Génétique, CHRU Reims, UFR de
médecine, Reims, France, 8 Institute for Child Health, London, United Kingdom,
9 Academisch Medisch Centrum, Amsterdam, The Netherlands, 10 Division of
Medical Genetics, University of Pennsylvania School of Medicine, Philadelphia,
PA, United States, 11 Institut für Humangenetik, Universitätsklinikum Schleswig-
Holstein, Lübeck, Germany, 12 NW Thames Regional Genetics Service, Kennedy
Galton Centre, Northwick Park and St Mark’s Hospitals, Harrow, United
Kingdom, 13 Department of Medical Genetics, Addenbrooke’s Hospital NHS
Trust, Cambridge, United Kingdom, 14 Service de Génétique Médicale, CHRU
Clermont-ferrand, Clermont-ferrand, France, 15 Cardiologie Pédiatrique, American
Memorial Hospital, CHU Reims, Reims, France, 16 Genetics department,
Lutheran General Children’s Hospital, Park Ridge, IL, United States, 17 Department
of Clinical Genetics, University Hospital of Leicester, NHS Trust, Leicester,
United Kingdom.
Background: Arterial tortuosity syndrome (ATS) is a rare autosomal
recessive connective tissue disease, mainly characterized by widespread
arterial involvement with elongation, tortuosity and aneurysms
of the large and middle-sized arteries. Recently, mutations were identified
in the SLC2A10 gene. This gene encodes the facilitative glucose
transporter GLUT10 and was previously suggested as a candidate
gene for diabetes mellitus type 2.
Methods: Twelve newly identified ATS families with 16 affected individuals
were clinically and molecularly characterized. In addition, extensive
cardiovascular imaging and glucose tolerance tests were performed
in both patients and heterozygous carriers.
Results and conclusions: All 16 patients harbor bi-allelic mutations in
SLC2A10 and haplotype analysis suggests founder effects for all 5
recurrent mutations.
In this series, patients are significantly older than those previously reported
in literature (p=0.04) and only one affected relative died, most
likely of an unrelated cause. Although the natural history of ATS seems
less severe, it does indicate a risk for ischemic events. Two patients
initially presented with a stroke, respectively at age 8 months and 23
years, due to a carotid artery dissection in the former. Tortuosity of the
aorta or large arteries is invariably present in all patients. Two adult
probands have mild aortic root dilation and 8 patients have arterial
stenoses. Heterozygous carriers do not show any vascular anomalies.
In 5 unrelated families, HbA1c levels and glucose tolerance tests
are normal in all 6 patients and 8 heterozygous individuals tested. As
such, overt diabetes is not related to SLC2A10 mutations associated
with ATS.
P0025. An Unusual Clinical Presentation Accompanying Cardiac,
Renal, Neurologic abnormalities with Asplenia
S. Unlubay 1 , O. Cogulu 2 , A. Alpman 2 , A. Anik 2 , A. Aykut 2 , F. Ozkinay 2 ;
1 Ege University Faculty of Medicine Department of Medical Genetics, Izmir,
Turkey, 2 Ege University Faculty of Medicine Department of Pediatrics, Izmir,
Turkey.
Congenital asplenia is mostly found in association with other anomalies,
particularly cardiac, hepatic, renal anomalies, and structural
abnormalities of the gastrointestinal tract. It is a feature of a number
of genetic disorders such as Stormorken syndrome, Kartagener syndrome
and particularly asplenia [Ivemark] syndrome. Asplenia syndrome
is the association of congenital absence of the spleen with a
variety of visceral abnormalities, predominantly of the cardiovascular
system. The incidence is estimated at 1 in 10.000 to 20.000 live births.
We report a 6-month-old female presented with multiple congenital
anomalies associated with asplenia and seizures with abnormal EEG
findings. She had macrocephaly, frontal bossing, microphtalmia, blue
sclera, long eyelashes, low set ears, broad base to nose, full cheeks,
long filtrum, cleft palate, micrognathia, hypoplastic nails, sacral dimple,
skin syndactyly of 2 nd ,3 rd ,4 th toes. She had a history of an operation for
congenital umbilical hernia after birth in newborn period and seizures.
Neurologic evaluation revealed motor retardation and hypertonicity.
Magnetic Resonance Imaging showed the cystic changes in germinal
matrix and agenesis of the corpus callosum. Atrial septal defect and
ventricular septal defect were detected in echocardiography. Abdominal
ultrasound showed hidronephrosis in the left side. Her karyotype
and subtelomeric FISH were normal. The combination of asplenia with
the anomalies detected in this case can be the variation of one of the
known asplenia syndromes or a new syndrome.
P0026. The MDR1 polymorphism C3435T in bronchial asthma
(BA) and steroid-resistant idiopathic fibrosing alveolitis (IFA)
patients
M. Simakova, Z.A.Mironova, V.I. Trofimov, E.D. Iantchina, M.V.Dubina, U.M.
Ilkovich;
I.P. Pavlov׳ State Medical University, St-Petersburg, Russian Federation.
The objective of this study was to estimate the frequency of polymorphism
C3435T of MDR1 gene occurrence and associations between
this polymorphism and features of glucocorticosteroids therapy. Blood
samples were taken from 55 asthmatics and 18 patients with steroidresistant
IFA. Genotypes were detected by PCR-RLFP. Frequencies
of MDR1 alleles C and T were not different - 0.55 and 0.45 in BA and
0.53 and 0.47 in IFA, respectively. Distribution of MDR1 genotypes
in BA were CC-36% (n=20), CT-40% (n=22), TT-24% (n=13); in IFA
were CC-17% (n=3), CT-72% (n=13), TT-11% (n=2). The frequency of
MDR1 CT genotype was higher in IFA (χ 2 =8.00, p=0.005). Daily doses
of oral glucocorticosteroids (GC) according to MDR1 genotypes in IFA
were: CC-15.0+7,6mg prednisolone, CT-24.6+1.7mg, TT-30+10mg
(no significant). Daily doses of inhalation glucocorticosteroids (iGC) in
BA group were: CC-955+106mcg, CT-941+113mcg, TT-1057+74mcg,
without significant too. But in patients with BA, which had daily dose
of iGC more than 800 mcg, genotype TT was found significantly often,
than in patients with smaller dose: 34%(n=13) versus 7%(n=1),
χ 2 =3,81, p=0,051.
Consequently, we found significant association of MDR1 CT genotype
with steroid resistant IFA. We assumed that asthmatics with MDR1 TT
genotype needed higher doses of iGC. It is related with possible role of
genetic control mechanism in corticosteroids transport from the cell.
P0027. New genetic variants of complex V,ATPsynthase 6&ATP 6
B. I. Radeva, E. Naumova, M. K. Stancheva;
University Children’s Hospital,Sofia, Sofia, Bulgaria.
Five new cases of genetic variants of mutation of ATP synthase 6 gene
were diagnosed with clinical and laboratory methods.The mutations
were identified by PCR method sequence of mitochondrial regions in
peripheral intravenose blood.The clinical symptoms,which help the diagnosis
were:microbrachicephaly,muscle hypotonia,normo to areflexia,
atrophy nervi optici and etc.The mental retardation was from light
motor retardation to generalized mental retardation. The investigated
mutation were unknown up to now and were not registrated in www.
mitomap.org yet. In the first case: base changes A91355G in ATP-synthase
6 gene,C9335T in CO III gene.In second case :base changes
T8538C MT ATP6gene ,transversion of aminoacid isoleucin / treonin.
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