Fragile X trinucleotide repeats from a normal population in Rio de Janeiro, Brazil.

Abstract

Fragile X, or Martin-Bell Syndrome is associated with a fragile site in the long arm of chromosome X, at Xq27.3. The incidence is ljl500 among males, and lj2500 in females. The major clinical features include mental retardation, macroorquidism, and craniofacial dysmorphology . The gene responsible for the disease, called FMR1, contains an expansion of a CGG repeat in the 5' untranslated region in its first exon (VERKERK et al. 1991). In the normal population the repeat size ranges from 6 to 54 copies (Fu et al. 1991). The normal transmitting male and some carrier females fall inside the pre-mutation category with allele sizes ranging from 43 to 200 copies. Above 200 copies it is considered a full mutation and people who have the repeat size in this range express the phenotypic characteristics of the syndrome (OOSTRA and WILLEMS 1995). Ultimately, the syndrome is characterized by the lack of the FMRl protein. It was suggested that 0.9 % of the normal population would have alleles in the pre-mutation size (ROUSSEAU et al. 1994). Based in the length, these alleles can be further divided in three groups: (1) small size (bellow 55 repeats), with a very low risk of expansion to a full mutation, (2) alleles in the size of 56-65 repeats, with 20-30%) risk of expansion to a full mutation, and (3) alleles with numbers of repeats greater than 90, with almost 100 YO risk of conversion to a full mutation. The allele expansion occurs during female meiosis leading to an unstable allele above 43 repeats (OOSTRA and HALLEY 1995). Another feature that contributes to the stability of the region is the presence of AGG interruptions after a stretch of 9 or 10 CGG. The lack of the interruption would predispose to the instability (EICHLER et al. 1995). Taking into account the global population, the number of repeats seems to be very constant, the major alleles being within the 29-30 repeat size (KUNST et al. 1996). It is well known that the Brazilian population is composed of, at least, three different ethnical groups, which are distinctly distributed throughout the country. At the beginning of the century, the south of Brazil received a major contribution from European Caucasians. The north and Northeast are composed, mainly, of native and African Americans. Due to economic reasons, the Southeast, which includes the Rio de Janeiro area, received people from all over the country and, at present, its population represents a mixture of people of different ethnic origin. Recently, nine VNTR markers for anonymous loci have shown no remarkable difference between the Brazilian population and the American Caucasian (MOURA-NETO and BU-