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

Clinical genetics
forms, and may go undiagnosed, especially in females. Hypoplasia of
one breast or a horizontal anterior axillary fold may be the sole clinical
manifestation of this syndrome.
Data here reported while adding further evidence of the genetic component
of the Poland’s syndrome and of the AD pattern of inheritance,
in the same time suggest a reduced penetrance and a variable phenotypic
expression of the disease.
P0222. Paternal deletion 15q11-q13 versus maternal disomy
- how different are these two Prader-Willi syndrome phenotypes
in a Polish cohort?
K. Spodar, A. Gutkowska, D. Jurkiewicz, K. H. Chrzanowska, M. Gajdulewicz,
H. Rysiewski, E. Popowska, M. Krajewska-Walasek;
The Children’s Memorial Health Institute, Warsaw, Poland.
We present the results of a study whose aim was to determine the impact
of a different genetic background on the phenotype of individuals
with Prader-Willi syndrome (PWS).
The molecular screening was performed in patients referred to our
centre with a clinical diagnosis of PWS. The patients were divided into
following groups: 25 with maternal disomy, 62 with de novo deletion
15q11-q13, 2 with deletion resulting from a balanced paternal translocation
and 3 with a microdeletion in the imprinting center (IC). Two
affected sibs inherited the microdeletion from their father and their paternal
grandmother was the carrier. The third child’s father was mosaic
for microdeletion which occured de novo. Forty seven patients with
normal methylation pattern at 15q served as a control group. Detailed
clinical investigations and data collected from the original questionnaire
enabled us to characterise each group.
Although there were many statistically significant differences between
patients from the control group and patients with confirmed PWS,
comparison of individuals with deletion and disomy showed only slight
differences. The children with disomy were taller, had longer trunk,
broader chest, milder dysmorphic traits, less severe behavioral problems
and started to walk earlier than those with deletion. The outcomes
of the study are discussed in view of a current literature. The characteristics
of cases with unbalanced translocations and IC microdeletion
will also be shown.
The work was supported in part by grant No 2PO5E06228 from the
State Cometee for Scientific Research of the Republic of Poland.
P0223. Genotype and Phenotype Analyses of Prader-Willi
Syndrome Patients in Taiwan
S. P. Lin 1 , H. Y. Lin 1 , C. K. Chuang 1 , C. Y. Huang 1 , J. L. Yen 2 , L. P. Tsai 3 , D. M.
Niu 4 , M. C. Chao 5 , P. L. Kuo 6 ;
1 Mackay Memorial Hospital, Taipei, Taiwan, 2 Branch for Women and Children,
Taipei City Hospital, Taipei, Taiwan, 3 Tzu-Chi Hospital in Xindian, Taipei, Taiwan,
4 Taipei Veterans General Hospital, Taipei, Taiwan, 5 Kaohsiung Medical
University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan, 6 National Cheng-
Kung University Hospital, Tainan, Taiwan.
Aim: To compare the genotype and phenotype correlation of patients
with Prader-Willi syndrome (PWS) in Taiwan.
Methods: We performed a retrospective analysis of 67 molecularly
confirmed diagnoses of PWS from January 1980 through July 2006 in
five medical centers in Taiwan. Clinical manifestations were compared
between the deletion and maternal uniparental disomy (UPD) groups.
Results: The genetic analysis identified deletion in 56 (84%), UPD in
10 (15%), and a probable imprinting center deletion or imprinting defect
in 1 (1%). Compared with UPD type, PWS patients with deletion
type were more likely to have the phenotypes of hypogonadism (p <
0.001), small hands and feet (p < 0.001), and hypopigmentation (p <
0.002). We also found a higher maternal age (p = 0.015) and a higher
paternal age (p = 0.021) in the UPD group. No other clinical features
were found to be significantly different between the two groups.
Conclusion: Our study in Taiwan is in contrast to most previous reports
in Western populations that indicated a higher incidence of UPD
in PWS. The possible subtle phenotypic differences between patients
with PWS on the basis of deletion type versus UPD type would be useful
both in clinical diagnosis and in understanding the genetic basis of
the subtypes of PWS.
P0224. Lack of Evidence of Monosomy 1p36 in Patients with
Prader-Willi-Like Phenotype
V. R. Rodriguez 1 , L. F. Mazzucatto 2 , J. M. Pina Neto 2 ;
1 Genetic department Medicine School of Ribeirão Preto, Ribeirão Preto, Brazil,
2 Genetic Department Medicine School of Ribeirão Preto, Ribeirão Preto, Brazil.
Some researchers suggested the existence of two possible phenotypes
for the 1p36 Monosomy. We would like to describe our experience
about the possible correlation between 1p36 microdeletion and
the Prader-Willi phenotype.
22 patients aged 8-23 years-old who tested negative for Prader-Willi
syndrome by Souther blot.
Clinical characterization of the patients was performed using a protocol
with the characteristics of 1p36 microdeletion Prader-Willi-Like
syndrome. Hight Resolution Cytogenetic Studies performed at a
550-850 bands level, and eleven polymorphic markers of 1p36 region
(D1S243, D1S468, D1S2660, D1S2795, D1S2870, D1S2145,
D1S214, D1S2663, D1S450, D1S244, D1S2667) were analyzed.
After cytogenetic analysis, no subtelomeric deletion was observed
over 40 metaphases by patients, and all the polymorphic markers for
1p36 were negative for microdeletions too.
According to the results, our sample is consistent with the Prader-Willi
phenotype (mental retardation/obesity 100% hyperphagia 86.4% developmental
delay 59% hypotonia 68.2% infant feeding problems 79%
abusive behavior 63%).
It also can be suggested that our methodology is adequate, 98% of the
1p36 microdeletions could be detected by high resolution cytogenetic
and, the number and position of the markers used which are located in
all six intervals suggested by Wu et al. 1999 observed clearly by Heislstedt
et al. 2003, even more we used 2 polymorphic markers inside the
obesity/hyperphagia chromosomal segment 1p36.33-36.32 (D’Angelo
et al. 2006).
The phenotype defined by Heilstedt et al. 2003 excluded hyperphagia/obesity.
Our results do not confirm the suggestion of D’Angelo et
al. 2006 about a specific hyperphagia/obesity chromosomal region in
1p36.
P0225. Detection of the G646C polymorphism of DYT1 gene in
patients with primary focal dystonia.
E. Sarasola 1 , F. Sádaba 2 , B. Huete 2 , M. García-Barcina 1 ;
1 Unidad de Genética del Hospital de Basurto, Osakidetza (Servicio Vasco de
Salud), Bilbao, Spain, 2 Servicio de Neurología del Hospital de Basurto, Osakidetza
(Servicio Vasco de Salud), Bilbao, Spain.
Introduction: Early-onset generalized primary dystonia is a dominantly
inherited movement disorder, mostly caused by a 3-bp (GAG) deletion
in exon 5 of DYT1 (TOR1A) gene encoding torsinA. It‘s penetrance is
estimated to be 30-40%. Moreover, in some families, members carrying
the same mutation could be either asymptomatic or display dystonia,
which may be focal, segmental, multifocal, or generalized in distribution,
suggesting the role of other genetics modifiers. It was shown that
cells expressing the G646C polymorphism in exon 4 of DYT1 gene
(replacement of aspartic acid with histidine at residue 216) developed
inclusions similar to those associated with GAG-deleted torsinA. The
aim of this study is to determine the putative role for this polymorphism
in primary focal dystonia.
Patients and Methods: Genomic DNA from 50 patients with focal primary
dystonia, in whom no GAG deletion in DYT1 gene had been
identified, was purified by „salting-out“ method. The detection of the
polymorphism was performed in an ABI PRISM 7500 Real-Time PCR
system using a validated TaqMan SNP Genotyping Assay from Applied
Biosystems. Data were analyzed with ABI PRISM Sequence Detection
Software.
Results and Discussion: 7 patients were heterozygotes G/C for G646C
polymorphism. The rest of the samples were homozygotes G/G and no
homozygotes C/C were identified. No relationship between the polymorphism
and the severity and evolution of the disease was found. In
order to complete this work, G and C allele frequencies will be studied
in healthy Basque Country population.
P0226. “Wiedemann-Rautenstrauch syndrome”: new case report
N. Rumyantseva, I. Naumchik, V. Kulak;
Republican Medical Centre “Mother and Child”, Minsk, Belarus.
We presented a clinical data of new case of “Wiedemann-Rautenstrauch
syndrome” (WRs) - a rare autosomal recessive disorder, mani-