2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
mutations in FBN1 and TGFBR2. The patient fulfils the clinical criteria
for MFS, but has extremely severe cardiovascular complications,
worse than observed in patients with TGFBR2 mutations only. Thus,
the molecular findings match the clinical features. In vitro studies investigating
these two mutations and their interactions are pending,
possibly providing a rationale for the choice of future medical treatment
in this patient.
Conclusion: In selected patients with features of MFS as well as features
suggestive of TGFBR2 mutations, DNA-analysis should include
FBN1 and TGFBR2.
P02.067
Neuhauser syndrome with novel findings: A case report of a rare
disorder
M. Seven1,2 , E. Yosunkaya1,2 , S. Yilmaz1,2 , K. Ender1,2 , G. S. Güven1,2 , A. Yuksel1,2
;
1 2 Cerrahpasa Medical Faculty, Istanbul, Turkey, Department of Medical Genetics,
Istanbul, Turkey.
Neuhaser Syndrome (Megalocornea-Mental Retardation) is a rare disorder
associated with major findings of hypotonia, mental retardation,
poor coordination, and megalocornea.
A 5 1/2 year -old-male patient referred to our department for atypical
facies and autism disorder. He had operations for congenital glaucoma
and cryptorchidism at 2 and 4 years old, respectively. He was severely
mentally retarded. He had yellowish white hair, frontal bossing,
downslanting palpebral fissures, strabismus, megalocornea, epicanthal
folds, anteverted nares, thin upper lip, narrow palate, low-set ears
with hypoplastic helixes. He also had long fingers, pectus carinatus,
widely spaced nipples, scoliosis, kyphosis, sacral dimple, pes planovarus.
Reduced deep tendon reflexes, ataxic walking and hypotonisity
were evident on neurological examination. Cranial MRI revealed
arachnoid cyst of posterior fossa, subependimal nodular heterotopies,
and left venous angioma. Abdominal ultrasonography, blood aminoacides,
urine organic acides, hearing examination were normal. Transillumination
defect of iris, retinal hypopigmentation, megalocornea (
right: 13 mm, left: 11 mm) and operated congenital glaucoma were
apparent on eye examination. Cytogenetic analysis revealed a normal
male karyotype with 46,XY. The examination findings clinically confirmed
the diagnosis of Neuhauser syndrome.
In conclusion, we report a case of Neuhauser syndrome with novel
findings of ventricular nodular heterotopia, congenital glaucoma, retinal
hypopigmentation, and albinismus-like appearance, which developed
during the course of the disease.
P02.068
Genomic aberrations in relation to unexplained mental
retardation in Estonian patients
K. Männik 1 , O. Žilina 1 , S. Parkel 1 , P. Palta 1 , H. Puusepp 1,2 , A. Veidenberg 1 , K.
Õunap 2,3 , A. Kurg 1 ;
1 Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia,
2 Department of Pediatrics, University of Tartu, Tartu, Estonia, 3 Department of
Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
Mental retardation (MR) affects 1-3% of population. This heterogeneous
disorder is caused by genetic, epigenetic and environmental
factors solely or in their combination. Despite extensive investigations,
the underlying reason(s) remain unknown in approximately half of the
MR patients and molecular basis of the pathogenesis is still poorly
understood.
In order to find out causative factors in Estonian patients with idiopathic
MR and to help to shed light on underlying molecular mechanisms,
we have collected a cohort of 250 unexplained MR patients and unaffected
members from 90 families.
To screen genomic aberrations potentially related to the clinical phenotype
we have applied Infinium Human370CNV SNP-arrays.
In 14 out of 76 (18%) families analysed to date we have found aberrations
with putative clinical significance, ranging in size from 0.5 to 8.3
Mb. These either affirm recently described microdeletion (like 15q13,
17q21.3) or microduplication (for example 7q11.23) syndromes or are
less characterized regions with potential clinical significance.
More detailed characterization of these genomic regions as well as
investigation how these imbalances influence expression in relations
to etiology of MR is currently our main interest.
P02.069
A new entity: Report on two siblings with mental retardation
A. Aykut, O. Cogulu, B. Durmaz, F. Ozkinay;
Ege University, Faculty of Medicine, Izmir, Turkey.
Two siblings, 17-year-old female and 13-year-old male, born to consanguineous
parents, were referred to the department of genetics because
of having short stature, motor-mental retardation and complete
absence of speech. On physical examination, both siblings had short
stature, a prominent and hairy forehead, thick eyebrows, synophrys,
acneiform scars on their faces, short and webbed neck, short hands
and feet were present. Laboratory data including urine amino acid
chromatography was normal, methylmalonicacid and dinitrophenylhydrazine,
serum IGF-1 and IGF-BP3 levels were normal. Abdominal
ultrasound was normal except mild splenomegaly. Skeletal survey was
normal except coxa valga. Cranial MRI and echocardiography were
not indicative for an abnormality. Cultured fibroblasts showed normal
neuraminidase, beta hexozaminidase, beta galaktosidase activity.
Enzymatic analyses of leucocytes a-iduronidase, β -glucuronidase,
β-galactosidase, α -fucosidase, α-mannosidase, N-asetil glucosaminidase,
glucosamine N-asetil transferase showed normal activity.
Sialotransferrin pattern was normal and cases were not compatible
with carbonhydrate deficient glycoprotein syndrome. Karyotypes were
normal. The siblings were not compatible with any identifiable genetic
syndrome, and they could be an example of a new clinical picture.
P02.070
Etiology of Mental Retardation in Brazil: The first 200
instituonalized patients
J. M. Pina-Neto, L. M. Batista, L. Mazzucatto, D. D. Ribeiro, A. C. Silva;
School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil.
We have studied 200 mentally retarded (MR) patients from two Brazilians
centers; 6% had mild , 48.5% moderate , and 37.5% severe MR.
There were 114 male (57%) and 86 female(43%). Their ages varied
from 6 month to 69 years, included 55.5% 0-15 years old, 42% 16 to
60 years old and, 2.5% > 60 years old.
It was impossible to perform the etiological diagnosis in 42 patients
(21%); the environmental causes were established in 85 patients
(42.5%); genetic diseases were diagnosed in 64 patients (32%). Chromosomal
anomalies were detected in 28 patients (14%), including 24
cases of Down syndrome (12%) and 4 structural chromosomal anomalies.
Genic abnormalities were detected in 29 patients (14.5%) with 6%
(12 patients) presenting autosomal recessive , 0.5% ( 1 patient) with
autosomal dominant , 1%( 2 patients) with X-linked diseases , one of
them (0.5%) affected by fragile X syndrome ; 1 patient (0.5%) with
imprint defect (Beckwith-Wiedemann syndrome); and, we detected 13
families (6.5%) with pure mental retardation. We detected 8 patients
(4%) of isolated CNS primary malformations and, 6 cases (3%) of inborn
errors of metabolism ( 4 cases of phenilketonuria). The environmental
causes (42 cases=21%) were: 33 patients (16.5%) with MR
due to isquemic-hypoxic perinatal accident; 28 patients (14%) MR due
to complications of prematurity; 11 patients (5.5%) MR due to prenatal
infections and, 7 patients (3.5%) MR due to postnatal infections; and,
5 patients (2.5%) MR due to Fetal Alcohol syndrome.
P02.071
the clinical importance of the variability of tRNALys and its
neighbouring mtDNA sequence
M. Molnar, K. Pentelenyi, V. Remenyi, Z. Pal, B. Bereznai, A. Gal;
Clinical and Research Centre for Molecular Neurology, Semmelweis University,
Budapest, Hungary.
Background: The mtDNA has a big variety, this proves the pathophysiologically
importance of the mtDNA-alterations. Pathogenic mtDNA
mutations are frequently found in tRNA coding regions of the mitochondrial
genome. The tRNA Leu gene is one of the hot-spots of the mtDNA.
Many pathogenic mutations have been reported in tRNA Lys too.
Design/Methods: The most common mtDNA mutations were investigated
in 470 patients, presumably with mitochondrial disease and in
100 controls with PCR-RFLP methods in the region of tRNA Lys and the
intergenic region of COII and tRNA Lys genes. In patients, whose restriction
patterns differed from the normal, bidirectional sequencing of this
region was performed.
Results: The A8344G mutation was found in 8 cases. In one family
(5 people) heteroplasmic substitutions T8312A and T8313G were