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

Clinical genetics
brachydactyly and generalized hypotonia. Discussion: Trisomy 18, is
the second most common autosomal trisomy in newborns. The frequency
of the associated findings are: heart (38.1%), gastrointestinal
(25.4%), limb (24.6%), head (20.3%), eye (11%) and genital anomalies
(9.3%). Conclusion: We present a case with trisomy 18, showing
unusual clinical findings. This case should make us to be careful at
the time to establish the diagnosis and to suspect a chromosomopaty.
By the wide clinical spectrum of this syndrome the karyotype give the
final diagnosis.
P0259. A novel mutation in SLC19A2 gene in an Iranian patient
with TRMA syndrome.
S. Zare 1,2 , b. keikhaei 3,4 , f. mahjoubi 1,5 , M. T. akbari 1,6 ;
1 Akbari Medical Genetic labaratory, No.98, Taleghani Street, Tehran, Islamic
Republic of Iran, 2 Islamic Azad Unversity Science and Research Campus,
Tehran, Islamic Republic of Iran, 3 Faculty of Medicine, Ahwaz Medical Science
University, Tehran, Islamic Republic of Iran, 4 Ahwaz Research Center for Thalassemia
and Hemaoglobinopathy, Tehran, Islamic Republic of Iran, 5 National
Research Center for Genetic Engineering & Biotechnology, Tehran, Islamic
Republic of Iran, 6 Department of Medical Genetics, Tarbiat Modares University,
Al-Ahmad Expressway, Tehran, Islamic Republic of Iran.
Thiamine - Responsive Megaloblatic Anemia (TRMA) or Roger syndrome
is a rare autosomal recessive disorder with childhood onset.
This disorder is characterized by the occurrence of multiple clinical
manifestations including megaloblastic anemia, diabetes mellitus and
sensorineural deafness, responding in varying degrees to thiamine
treatment. The gene SLC19A2 which codes for a thiamine transporter
is responsible for this syndrome and it is located at chromosome
1q. To date 15 different mutations have been reported in 28 families
worldwide. Here we present a new case with a novel mutation, a 20
years old male patient with characteristic features of TRMA with good
response to thiamine therapy. His SLC19A2 gene was screened by
direct sequencing and a single nucleotide base substitution in homozygous
form was found. This mutation leads to a premature stop codon
(W233X), and can be considered diseases causing because of its
nature. Considering the limited number of affected cases reported so
far in the literature, it is evident that TRMA is a very rare condition with
heterogenous molecular basis. As far as its distribution is concerned,
out of 28 reported TRMA families worldwide, five families including this
present case are from Iran who had different mutations. The rest of the
patients were from Indian subcontinent (India, Kashmir and Pakistan)
suggestive of higher frequency in Asian populations.
P0260. Six pregnancies in a woman with Turner syndrome,
including a case of holoprosencephaly
E. S. Ramos1 , A. Araújo1 , C. D. Martinhago1 , L. R. Martelli1 , R. M. Reis1 , D. G.
Melo2 ;
1 2 University of São Paulo, Ribeirao Preto, Brazil, Federal University of São
Carlos, São Carlos, Brazil.
Ovarian failure is a typical feature of Turner syndrome (TS). Only 2%
of these patients (pure 45,X or mosaic) have natural pregnancies.
Furthermore, these pregnancies have been plagued not only by chromosome
anomalies and fetal malformations, but also by spontaneous
abortions. We report an unusual case of a woman with TS and
chromosome mosaicism (karyotype 45,X[2]/46,X,r(X)[4]/46,XX[94])
and normal fertility. At 12 years and 6 months of age, her height was
127.5cm and she was forwarded to a clinical evaluation due to short
stature. Menarche was at age 13 years and her menstrual cycle had
varied from 25 to 30 days. At 24 years of age, she has had six documented
pregnancies, including one child with holoprosencephaly with
normal karyotype. For patients with TS and spontaneous puberty, genetic
counseling and prenatal diagnosis are indicated.
P0261. Turner Syndrome mosaicism: an unusual case with
a large dicentric marker chromosome: 45,X/46,X,der(X), ter
rea(X;X), de novo.
A. Nucaro 1 , P. Melis 2 , M. Casini 3 , R. Rossino 4 , M. Cau 4 , R. Congiu 4 , M. Melis 4 ,
S. Loche 3 ;
1 Istituto di Neurogenetica e Neurofarmacologia, Monserrato( Cagliari), Italy, 2 Dipartimento
di Scienze Pediatriche e Medicina Clinica, University Cagliari, Italy,
3 (2) Servizio di Endocrinologia Pediatrica,, Ospedale Regionale Microcitemie,
ASL8 Cagliari, Italy, 4 (4) Dipartimento di Scienze Biomediche e Biotecnologie,
University Cagliari, Italy.
Turner’s Syndrome(TS) is characterized by the total or partial absence
of one normal second X chromosome. TS occurs in 1/2500-3000 liveborn
females. The phenotype is variable and include short stature and
gonadal dysgenesis. Approximately 50 percent of the patients has a
45,X0 karyotype with no second sex chromosome, and 5 to 10 percent
have a duplication (isochromosome) of the long arm of one X. Most of
the remaining cases involves mosaic karyotypes in which only a proportion
of cells is 45,X, with one or more additional cell lineages.
X/X translocations are quite rare in man. The effect of this anomaly on
the phenotype depends on the amount of deleted material and whether
the chromosomes are joined by their long or short arm.
We report an unusual case of Turner’s Syndrome mosaicism in a sixteen
year old girl, who was referred to our Institution for primary amenorrhea
and short stature. Endocrine evaluation revealed hypergonadotropic
hypogonadism, which required a study of the karyotype. Cytogenetic
analysis, performed on peripheral blood leucocytes, showed
a 45,X/46,X,der(X),ter rea (X;X)de novo karyotype. The prevalent cell
line was 45,X(90% cells). A second cell line(10% cells) showed a very
large marker chromosome, similar to a large metacentric chromosome.
FISH and molecular analysis revealed that the marker chromosome
was dicentric and totally derived from the paternal X chromosome.
To the best of our knowledge, this is the first reported case of
TS mosaicism with a marker 45,X/46,X,der(X), de novo, that has been
characterized by molecular and FISH analysis.
P0262. Molecular investigation of Angelman and Prader Willi
syndromes. Screening for UBE3A mutations: preliminary results
E. Tzagaraki1,2 , C. Sofocleous1 , S. Kitsiou1 , H. Frysira1 , G. Goulielmos2 , E.
Kanavakis1 , A. Mavrou1 ;
1 2 University of Athens, School of Medicine, Athens, Greece, University of Crete,
School of Medicine, Herakleion, Greece.
Molecular defects within chromosomal region 15q11- q13, which contains
genes regulated by the imprinting centre (IC), are responsible
for Angelman (AS) and Prader Willi (PWS) syndromes. Differentially
methylated regions of the IC play a major role in the establishment
of the methylation pattern and genomic imprinting of the locus. PWS
is considered a “contiguous gene syndrome”, while UBE3A imprinted
gene has been implicated as the AS gene, since genomic mutations
of which have been identified as the sole molecular defect in AS patients.
Routine molecular analysis with Methylation Specific PCR and Dinoucleotide
Repeat Polymorphism analysis was performed in 185 patients
referred for AS (87) and PWS (98).The diagnosis was confirmed in
11 AS and 16 PWS patients. 30 patients referred for AS were further
analyzed by mutation screening of the UBE3A gene by automated sequencing
of exons 9,12, 15 and 16.
Large deletions were excluded by the presence of the expected PCR
product and no mutations were identified.
4- 6% of AS patients are predicted to have mutations in UBE3A gene,
most of which are located in exons 9, 12, 15, 16. Since 75- 80% of
these mutations are familial characterization of the defect and genetic
counselling are essential. Although this study, has not as yet detected
any mutations, further screening of all exons of UBE3A, as well as
other genes, related to AS like phenotypes (MECP2 gene) will probably
identify mutations, confirming the clinical diagnosis and providing
information about the molecular mechanisms.
P0263. The “characteristic” clinical phenotype of maternal
UPD(14): does it really exist? A clinical, cytogenetic, and
molecular study of three new unrelated subjects
M. Giovannucci Uzielli1 , N. Dayan1 , L. Giunti2 , S. Guarducci2 , V. Gimino1 , A.
Zeffiri1 , E. Lapi2 , U. Ricci2 , M. Ottaviani1 , M. Isoldi1 , G. Scarselli1 ;
1 2 University of Florence, Florence, Italy, Children’s Hospital “Anna Meyer”, Florence,
Italy.
Maternal uniparental disomy for chromosome 14 [UPD(14)mat] is firmly
associated with abnormal phenotypes, including pre- and postnatal
growth retardation, features overlapping PWS, and other abnormal
clinical aspects. The presence, in a diploid genome, of a chromosome
pair (or of a chromosome fragment) derived from one genitor, carries
two main types of developmental risk: the occurrence of an imprinting
disorder, or the inheritance of a duplicated mutant of a recessive trait
leading to the homozygosity (Engel E., 2006).
2