Transcript Diapositiva 1

MOLECULAR DIAGNOSIS OF FRAGILE X SYNDROME: A COMPILATION OF DATA
OF 4,238 PATIENTS AND RELATIVES FROM 849 FAMILIES IN SPAIN
M.Isabel Tejada (1); Josep Artigas (5); Antonio Bellón (2); Isabel Fernández-Carvajal (8); Yolanda
De-Diego (9); Guillermo Glover (7); Miriam Guitart (5); Francisco Martinez (4); Monserrat Milá (3);
Feliciano Ramos (6).
(1) Cruces Hospital (Barakaldo-Basque Country); (2) GIRMOGEN; (3) Clinic Hospital (Barcelona-Catalonia); (4) La Fe
Hospital (Valencia); (5) Parc-Taulí Hospital (Sabadell-Catalonia); (6) Medicine Faculty ( Zaragoza-Aragón). (7) Virgen de
la Arrixaca Hospital (Murcia); (8) IBGM (Valladolid-Castilla); (9) Carlos Haya Hospital (Málaga-Andalucía); SPAIN.
INTRODUCTION
Fragile X syndrome (FXS) is caused by a full mutation (FM) in the FMR1 gene and is the most common form of inherited intellectual
disability. The prevalence of the FM has been estimated to be in Spain around 1 in 6000 males, but the real number of individuals with
FM or Premutation (PM) is still unknown in the majority of countries, not only in Spain.
It is a family of disorders which affects both males and females being females more mildly affected, and, in the case of males, there is
a broad range of features which includes a spectrum from a very mild phenotype to fully affected, but the exact frequencies of the
clinical involvement remain unknown in most of the populations studied.
Both males and females can be "carriers" of the Fragile X gene and pass it on to their children. Furthermore, carriers of the FMR1 gene
can develop: female carriers ovarian insufficiency, infertility and early menopause (FXPOI) and male (and less frequently female)
carriers an adult onset neurological condition called FXTAS.
OBJECTIVES AND METHODS
Grupos 1 y 2
To know the number of FXS cases and families in Spain, and to obtain clinical data of FM
patients and PM carriers, we (the GIRMOGEN group) created a registry in collaboration
with the Spanish Federation of FXS Families and with the “Real Patronato de la
Discapacidad”, a Royal trust for disabilities presided over by the Spanish Queen. With
the aim of adding some new data about FXS families in the world, we will present in the
Conference the data collected in our database from 1991 until the end of 2008.
GIRMOGEN
SPAIN
RESULTS
Nowadays our registry contains 4,238 postnatal and prenatal cases belonging to 849
families. A total of 1,363 FM and mosaic patients (864 males and 499 females have been
recorded. All FXS males have mental retardation and 65% of FXS females have mental
impairments. Tables below summarizes the statistical, molecular and clinical findings of
the cases, studied molecularly between 1991 and 2008. Median age at diagnosis of the
proband was 16,6 years, because in the last years, probands with FXTAS and with FXPOI
have increased this median. In relation to these individuals with PM, 96 women have
FXPOI and, interestingly, 2 mosaic women and one FM women as well. With regard to
FXTAS, a total of 38 cases have been recorded, 17 of them women. The median age of
onset was 65,2 years for men and 70,7 years for women.
1991
Probands
Total cases studied
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008 TOTAL
32
25
57
59
45
30
30
44
44
54
45
35
62
61
46
41
41
771
165
209
169
198
218
188
164
147
185
189
192
209
143
194
232
155
169
202
3328
Individuals studied each year
Probands
250
1200
1000
Total cases studied
FM
Mosaics
PM (55-199)
Cases
Table 2 and Figure 2:
Distribution of individuals
studied by sex and
molecular diagnosis.
20
Table 1 and Figure 1:
Distribution of individuals
studied by year.
Individuals studied
FM
800
Mosaics
600
PM (55-199)
Others
400
Intermediate (45-54)
200
Normal (<45)
0
Males
Females
Sex
Others
Intermediate (45-54)
Normal (<45)
TOTAL
Males
779
85
275
1
25
636
1801
Females
455
44
1169
1
47
701
2417
TOTAL
1234
129
1444
2
72
1337
4218
200
150
100
50
Figures 2 and 3: Clinical characteristics of FXS patients distributed by sex
08
20
07
06
20
05
20
04
20
03
20
02
20
01
20
00
20
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
19
91
0
Years
Table 3: Percent expansion to FM with transmission of maternal PM allele
Maternal repeat size Offspring with PM
Offspring with FM
Physical and other Behavioral Features
Behavioral Phenotypes
% of expansion
100,0%
90,0%
80,0%
70,0%
60,0%
50,0%
40,0%
30,0%
20,0%
10,0%
0,0%
90,0%
80,0%
70,0%
60,0%
50,0%
40,0%
30,0%
20,0%
10,0%
0,0%
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DISCUSSION
According to the total population in Spain and to the previously estimated
prevalence of FXS in Spain (Millán et al., 1999), we have recorded 1/4 of
the FSX cases in our country. This large amount of cases gives a high
statistical power to analyze in depth all of these data and so we will do
this analysis in the next months.