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

Clinical genetics
an indication of the presence of FMR1 mRNA in female patients, which
might have clinical implications regarding subsequent therapy.
P0114. Prevalence of Fragile X Premutation and Intermediate/
Grey Zone Alleles in a Basque Sample
I. Arrieta Saez 1 , O. Peñagarikano 2 , M. Telez 1 , L. Valverde 1 , B. Criado 3 , J.
Ramirez 1 , B. Ortega 1 , A. Gonzalez 4 , P. Flores 5 , C. Lostao 1 ;
1 Department of Genetics, Faculty of Science and Technology, University of the
Basque Country, Bilbao, Spain, 2 Departments of Human Genetics, Emory University
School of Medicine, Atlanta, Georgia, 3 High School Da Maia, CESPU,
Porto, Portugal, 4 Department of Internal Medicine, Faculty of Medicine, Basque
Country University., Bilbao, Spain, 5 Department of Nursery, School of Nursery,
University of the Basque Country, Bilbao, Spain.
The Fragile X Syndrome (FXS; OMIM: 309550) is the most common
inherited form of mental retardation. The molecular basis is usually the
unstable expansion of a CGG trinucleotide repeat in the FMR 1 gene
witch resides at chromosome position Xq27.3 and is coincident with
the fragile site FRAXA.Based on the size of CGG secuence individuals
are classified as having normal (6-54 CGG), premutation (55-200
CGG) and full mutation alleles (>200 CGG). In adition the term intermediate/grey
zone alleles has been used to define alleles with sizes
at high range of normal alleles (35-54 CGG). Our previous cytogenetic
and molecular screening for Fragile X Syndrome among mental retarded
people of Basque and no Basque origin showed and absence
of full mutation among Basque Sample. In the present work we analized
the prevalence of FMR 1 premutated and intermedite/grey zone
alleles, because recent clinical and molecular studies have changed
the view that premutated alleles serve only as a source for full mutation
alleles in transmision of FXS and that functional and phenotyphic
effects are not associated with FMR 1 repeat size in the high end of
the normal range alleles. A total of 298 unrelated male individuals were
included in this study. The results obtained showed that the estimated
prevalence of the intermediate/grey zone alleles 1/10 in Basque males
(7.32 %) was lower than that reported in Caucasian populations. The
prevalence of premutation alleles is 1/298 in males. The prevalence
of premutation alleles in the general populated is estimated in 1/813
males.
P0115. 47,XYY male with the fragile X syndrome: rare genetic
assotiation
M. Simandlova, D. Novotna, Z. Musova, M. Havlovicova;
Institute of Biology and Medical Genetics, Charles University Second Medical
School and University Hospital Motol, Prague, Czech Republic.
We report on a 26 year-old developmentally disabled man referred to
our clinic for evaluation because of pregnancy of his younger sister.
Cytogenetic and molecular analysis revealed a 47, XYY karyotype and
the presence of a trinucleotide repeat expansion resulting in fragile
X syndrome. Direct detection of the pre- and full mutation for the affected
individual and his at-risk female relatives were performed . To
our knowledge, this is the third report of concurrence of XYY and fragile
X syndrome in the medical literature ( but one of these patients was
46,XY/47,XYY mosaic male with fragile X syndrome) . Review of sex
chromosome abnormalities associated with fragile X syndrome and
phenotypic considerations are presented.
This work is supported by the Grant number: 00000064203-MZCR.
P0116. Cardiac evaluation of 34 individuals with Fragile X
Syndrome
M. Alikaşifoğlu, Y. Alanay, D. Alehan, G. Utine, B. Volkan-Salancı, K.
Boduroğlu, D. Aktaş, E. Tunçbilek;
Hacettepe University, Ankara, Turkey.
Fragile X syndrome is the most common inherited cause of mental
retardation. Patients with fragile X syndrome have cardiac defects
similar to those seen in other disorders of connective tissue such as
Marfan’s syndrome and Ehlers-Danlos syndrome. These, and other
somatic features, suggest an underlying connective tissue dysplasia.
The underlying connection between Fragile X Mental Retardation
Protein (FMRP) and the connective tissue dysplasia seen in FXS is
still unclear. The limited numbers of studies evaluating cardiovascular
aspects of FXS have yielded different results. In this study, transthoracic
echocardiogram and ECG were available in 34 male participants.
Mean age was 9,17 years [2-34 yrs]. There were two adult patients,
one with mitral valve prolapsus (MVP), the other with aortic insuffi-
ciency. The mean age of participants under 18 years was 8,06 (the
eldest 17 years old). We compared our results with the data provided
in the largest study yet (n=40) by Loehr et al. (1986). The comparison
suggests that the prevalence of MVP is somewhat lower 8/32 (25%)
in our study, while it was 35.2% in the latter, with a similar mean age
of 8.6 years, while aortic annulus dilation was higher in the current
study, 5/32 (15,6%) versus (10%). There was no significant correlation
between metacarpophalangeal joint hyperextensibility and MVP. This
data supports previous recommendations towards routine echocardiographic
evaluation in individuals with FXS. Re-evaluation of the same
group especially follow-up measurements of aortic annulus diameters
in our ongoing longitudinal study will reveal the natural history of cardiac
complications in FXS.
P0117. Audiological evaluation of 63 males with Fragile X
D. Aktas, Y. Alanay, G. Utine, B. Volkan-Salancı, A. Genç, F. Başer, S. Sevinç,
U. Akyol, K. Boduroğlu, M. Alikaşifoğlu, E. Belgin, E. Tunçbilek;
Hacettepe University, Ankara, Turkey.
Fragile X syndrome is the most common inherited cause of mental
retardation. Medical problems other than cognitive and behavioural issues
have been rarely addressed in individuals with FXS.
In this study 36 individuals molecularly diagnosed with FXS were evaluated.
Mean age of the participants was 8,41 yrs [1,5-27]. Median IQ
score was 45 [25-103] Seventy-two percent were having occupational
therapy, while 25% also attended a public school.
ENT examination revealed cerumen in 12 (33%), opaque ear drum in 4
(11%) Audiologic evaluation revealed normal hearing in 29 participants
(80,5), while 7 (19,5) had minimal conductive type hearing loss. In general
, infants from birth to 6 months underwent observation audiometry;
children between 6-36 months of age underwent Visual Response Audiometry
(VRA) in soundfield; and children 36 months of age and older
underwent play audiometry in soundfield or with earphones according
to the degree of the child’s cooperation. Cooperation problems due
to mental retardation affected this rule negatively. 19 non-cooperative
patients (52,78%)(age range 7-27 yrs) were tested by VRA or play
audiometry. In 7 patients(19,45%), suprathresholds responses were
observed. For these patients, objective test methods were used effectively
for final decision. There was no correlation between IQ scores
and hearing status. Objective test methods were more feasible for diagnose
in patients with Fragil X syndrome. Mean age at diagnosis was
significantly lower in the group with hearing loss. This may reflect the
earlier referral to a physician with recurrent infection or speech delay
may have prompted earlier diagnosis.
P0118. Fragile X syndrome in Estonia
H. Puusepp 1,2 , T. Kahre 3 , I. Lind 3 , E. Raukas 3,4 , V. Soo 3 , H. Sibul 1,4 , A. Kurg 1 , K.
Õunap 2,3 ;
1 Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia, 2 Department
of Pediatrics, University of Tartu, Tartu, Estonia, 3 United Laboratories,
Tartu University Hospital, Tartu, Estonia, 4 Estonian Biocentre, Tartu, Estonia.
The Fragile X syndrome is the most common human chromosomal
monogenic disease associated with heritable mental retardation, and
is the second most frequent cause of mental retardation after Down
syndrome. Our study consists of the screening of 561 Estonian children
having mental retardation, autism, delayed speech and/or behavioral
problems. The patient samples were sent to the United Laboratories
of Tartu University Hospital for screening of fragile X mutation from
year 1997 to 2006. The molecular study for the diagnosis has been
performed by two different techniques. During 1997-2001 the Southern
blot analysis and later PCR with fluorescently marked primers followed
by CGG repeat length detection at ABI PRISM 377 was used.
Among 561 (477 boys/84 girls) patients we found 15 full mutations
(14 boys/ 1 girl), and 1 premutation in a girl. The main indication for
the analysis in diagnosed boys was mental retardation in 11 patients,
autism in 2 patients, and characteristic phenotype in 1 patient. The girl
with a full mutation was investigated due to psychomotor retardation
and delayed speech. The girl with a premutation had mild mental retardation
and primary ovarian failure. The birth prevalence of full mutation
in FMR1 gene causing fragile X syndrome is 1 in 25,308 among
individuals born during 1984-2006. We found that birth prevalence of
the fragile X syndrome is significantly lower in Estonia than in other
countries. The reason for that is still unknown for us.
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