Fragile X syndrome is the most common inherited form of mental retardation. The syndrome is associated with a CGG repeat expansion in the 5'UTR of the first exon of the FMR1 gene. This gene maps to Xq27.3 and coincides with the cytogenetic fragile site (FRAXA). The present study deals with the prevalence of fragile X syndrome among individuals with mental retardation of unknown cause from institutions and special schools from the Spanish Basque Country. Results of cytogenetic and molecular studies, performed in a group of 134 unrelated individuals (92 males and 42 females) are presented. The cytogenetic marker at Xq27.3 was identified in 12 patients. Other chromosomal abnormalities were found in two cases that this and previous studies confirmed as Angelman and Prader-Willi syndromes. Two males, in whom the cytogenetic marker was identified, were found negative for FRAXA and FRAXE expansion at the molecular level. The present study shows that the frequency of the FRAXA full mutation in individuals of Spanish non-Basque origin is in the range of other Spanish populations. In the sample of Spanish Basque origin we have not found cytogenetic FRAXA site expression, and the CGG repeat size of FMR1 gene is in the normal range. The significance of these results are discussed.
"Preliminary investigations have suggested that Spanish Basques are less prone to develop fragile X syndrome, given the stability of the FMR1 gene (lower frequency of large alleles) (Arrieta et al. 1999). However, the same team has recently analyzed the CGG repeats within this gene using a different sample and have found that the prevalence of potentially unstable alleles is comparable to that of other European populations (Peñagarikano et al. 2004). "
[Show abstract][Hide abstract] ABSTRACT: The Basques live at the western end of the Pyrenees along the Atlantic Ocean and are thought to represent the descendants of a pre-Neolithic people. They demonstrate marked specificities regarding language and genetics among the European populations. We review the published data on the population genetics and Mendelian disorders of the Basques. An atypical distribution in some blood group polymorphisms (ABO, Rhesus, and Duffy) was first found in this population. Subsequently, additional characteristics have been described with regard to proteins (enzymes and immunoglobulins) and the HLA system. The advent of molecular biology methods in the 1990s allowed further insights into Basque population genetics based mainly on Y-chromosome and mitochondrial DNA. In addition, the Basques demonstrate peculiarities regarding the distribution of various inherited diseases (i.e., unusual frequencies or founding effects). Taken together, these data support the idea of an ancient and still relatively unmixed population subjected to genetic drift.
Human Biology 11/2005; 77(5):619-37. DOI:10.1353/hub.2006.0001 · 0.85 Impact Factor
"absence of the full mutation among Basque population [Arrieta et al., 1999a]. Subsequent investigations on FMR1 gene among Basques showed a low frequency of large alleles and the maintenance of AGG interruptions on them [Arrieta et al., 1999b]. "
[Show abstract][Hide abstract] ABSTRACT: The expansion of a trinucleotide repeat [CGG]n located in the FMR1 X-linked gene is the main cause of fragile X syndrome, the most common form of inherited mental retardation. We have analyzed the factors known, to date, to influence the instability of the repeat in 158 normal X chromosomes from the Spanish Basque population. These factors included length of the repeat, AGG interspersion pattern, length of uninterrupted CGG and DXS548-FRAXAC1 markers associated haplotype. Previous investigations on Basques showed an absence of this disorder among mentally retarded individuals that was likely due to a low prevalence of large CGG alleles and the presence of AGG interruptions on them. The present report suggests that, although the frequency of large alleles is low and they do maintain AGG interruptions, different mutational pathways that might lead to fragile X syndrome could be occurring among Basques. These pathways mainly include alleles with internal sequences 9 + 9 + n and 9 + 12 + 9 that show fragile X associated haplotypes. Besides, the lack of the most proximal AGG interruption, proposed recently as a novel factor involved in CGG repeat instability, was highly identified among alleles with long pure CGG tracts, which showed an internal sequence n + 9. The data suggest that, despite the lower incidence of large alleles, the prevalence of potentially unstable alleles among Basques is similar to that of other Caucasian populations and that these alleles could become fragile X chromosomes.
American Journal of Medical Genetics Part A 08/2004; 128A(3):250-5. DOI:10.1002/ajmg.a.30116 · 2.16 Impact Factor
"Haplotype construction with these markers has revealed linkage disequilibrium between the normal, stable alleles as well as the unstable CGG repeat alleles among individuals with fragile X syndrome in studies of European populations from France and Spain (Oudet et al, 1993a), Belgium and the Netherlands (Buyle et al, 1993), Northern Europe (Riggins et al, 1992), Italy (Chiurazzi et al, 1996a), United Kingdom (Macpherson et al, 1994), Sweden (Malmgren et al, 1994), Finland (Oudet et al, 1993b; Haataja et al, 1994; Zhong et al, 1996), Greece and Cyprus (Patsalis et al, 1999) and Denmark (Larsen et al, 1999, 2000). We recently investigated the prevalence of fragile X syndrome among mentally retarded individuals of Basque and non-Basque origin from institutions and special schools from the Biscay province in the Spanish Basque Country (Arrieta et al, 1999a). The results of cytogenetic and molecular analyses showed that the frequency of the FRAXA full mutation in individuals of non-Basque origin (10.20%) was in the range of other Spanish populations analyzed from institutions and special schools outside of Spanish Basque Country (6.40–12%). "
[Show abstract][Hide abstract] ABSTRACT: Fragile X syndrome is associated with an unstable CGG repeat sequence in the 5' untranslated region of the first exon of the FMR1 gene. The present study involved the evaluation of factors implicated in CGG repeat stability in a normal sample from two Basque valleys (Markina and Arratia), to discover whether the Basque population shows allelic diversity and to identify factors involved, by using the data in conjunction with previous findings. The study was based on a sample of 204 and 58 X chromosomes from the Markina and Arratia valleys, respectively. The CGG repeat, the AGG interspersion and two flanking microsatellite markers, FRAXAC1 and DXS548, were examined. In the Markina valley, gray zone alleles (> or =35 CGG repeats) were associated with anchoring AGGs, with the longest 3' pure CGG repeats of the valley (=15), with the 5' instability structure 9+n and with one principal fragile X FRAXAC1-DXS548 haplotype 42-50. In the Arratia valley, gray zone alleles (> or =35 CGG repeats) showed the highest frequency among the Basque samples analyzed, and were associated with anchoring AGGs, with the longest 3' pure repeats (> or =20), with the 5' instability structure 9+n and with one "normal" FRAXAC1-DXS548 haplotype 38-40 (these data from Arratia suggest the existence of a "protective" haplotype). The results showed, on the one hand, differences between Markina and Arratia in factors implicated in CGG repeat instability and, on the other hand, a great similarity between the general Basque sample from Biscay and the Markina valley.
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