2008 Barcelona - European Society of Human Genetics

Clinical genetics
Sapienza” University, Roma, Italy.
OPHN1 gene (MIM 300127) mutations are a well established cause of
a distinctive phenotype characterized by mental retardation of variable
degree, epilepsy, rostral ventricular enlargement and cerebellar hypoplasia
. Duplication of this region has never been reported .
We describe the first familial case of a Xq12q13.1 duplication of 800
kb encompassing the OPHN1 gene, detected by array-CGH . The proband
phenotype is characterized by facial dysmorphisms and severe
mental retardation associated to specific cerebral anomalies.
Our proband’s phenotype never prompted the hypothesis of oligophrenin
mutation. This might be due to the specific facial and NMR
appearance of OPHN1 mutated patients (deletions and point mutations)
. These patients are characterized by long face, wide forehead,
deeply set eyes, hypothelorism, long tubular nose, short philtrum and
prominent chin . The most striking hallmark shared by OPHN-1 patients
on NMR is posterior vermis dysplasia, including lobules VI and VII (declive,
folium, and tuber) partial agenesis associated with a supplementary
right vermian parasagittal cleft and a mild cerebellar hemispheris
dysgenesis . Instead our patient showed an altered signal in the sopratentorial
white matter that was more pronounced at the inferior and
posterior cerebral hemispheres . Lesions were also described in the
pontine tegmentum, corpus callosum, posterior arms of inner capsules
and central portions of pallidi nuclei .
To our knowledge this is the first report of a clinical phenotype associated
with duplication of Xp12 .
P01.082
syndromic X-linked mental retardation
A. Cueto González 1,2 , T. Vendrell Bayona 1,2 , M. Raspall 3 , I. Madrigal 4,5 , M.
Milà 6,5 , L. Pérez Jurado 1,2 ;
1 Programa de Medicina Molecular i Genètica, 08035 barcelona, Spain, 2 Hospital
Vall d’Hebrón, Barcelona, Spain, 3 Servei de neuropediatria. Hospital Vall
d’Hebrón, 08035 barcelona, Spain, 4 CIBERER. Servei de Bioquímica i Genètica
Molecular, Barcelona, Spain, 5 Hospital Clínic Barcelona, Barcelona, Spain,
6 Servei de Bioquímica i Genètica Molecular., Barcelona, Spain.
We report a new family with familiar mental retardation and seizures
with few dysmorphic facial features .
The proband was born at term after an uncomplicated pregnancy . The
boy was the first child from healthy non-consanguineous parents. At
the age of 3 years he was referred to medical geneticists for diagnostic
advice . The facial appearance was slightly dysmorphic with deeply set
eyes, strabismus, a large philtrum, retrognathia and prominent incisors
. He had generalised hypotonia, delayed psychomotor development
(walking at 3 years), he had no language (he only say few words
at 3 years) and significantly mentally retarded. He developed a first
epileptic insult during the second year . The metabolic screening and
the electroencephalogram were normal . His karyotype was normal,
46,XY .
On examination with 11 years old he had a brain magnetic resonance
imaging, it showed large ventricles without hydrocephalus, a large cisterna
magna with cerebellar hypoplasia .
He had a maternal uncle and maternal great-uncle with mental retard
and facial appearance similar . His maternal uncle had a test for fragile
X negative .
There was a syndromic X-linked mental retardation with cerebellar hypoplasia
. We revaluated the case with 11 years old and analyzed by
Multiple Ligation PCR Amplification (MLPA) in the probandus and his
mother, but it was not possible in the maternal uncle, with deletion in
the exons 3, 4, 5 and 6 of the oligophrenin-1 gene (OPHN1 gene) .
P01.083
New Rett syndrome and Fragile X syndrome clinical scales for
genotype-phenotype correlation studies
V. Y. Voinova 1 , I. Y. Iourov 1 , S. A. Tushkevich 2 , P. V. Novikov 3 , Y. B. Yurov 1 , S.
G. Vorsanova 3 ;
1 Mental Health Research Centre RAMS, Moscow, Russian Federation, 2 Moscow
University of Psychology and Education, Moscow, Russian Federation,
3 Institute of Pediatrics and Children’s Surgery, Moscow, Russian Federation.
To investigate genotype-phenotype correlations new clinical scales
were developed for providing quantitative measurements of 23 Rett
syndrome (RTT) and 24 Fragile X syndrome (FXS) phenotypic signs .
Scores for separate symptoms summarized to get a total phenotypic
severity score .
Correlations between MECP2 mutation type, position and phenotype
severity were found in 54 RTT patients. There were significant differences
with more severe phenotypic manifestations in patients with
truncating mutations compared with those with missense mutations in
the phenotype severity scores (P