Structure and stability upon maternal transmission of common and intermediate FMR1 (Fragile X Mental Retardation 1) alleles in a sample of the Brazilian population

ABSTRACT

In order to investigate the stability of the FMR1 (Fragile X Mental Retardation 1) alleles from the normal population, when maternally inherited, we analyzed 75 mother-to-son transmissions. Sixty-eight alleles fell within the common range with 20-40 CGG repeats, and seven alleles were intermediate, with 41-48 repeats. No change was observed either in the length or in the structure of these repeats upon transmission. Fifty-three alleles were ascertained in different families, and their size distribution was similar to those described for European and European-derived populations, with three peaks of frequency 66 percent of the alleles with (CGG)29, (CGG)30 or (CGG)31, 7.5 percent with (CGG)20, and 5.7 percent with (CGG)23. Regarding the AGG interspersion pattern, 69.8 percent had two AGG repeats, 20.8 percent had one, 5.7 percent had three and 3.8 percent had none. The most common patterns were 10+9+9 (30.2 percent), 9+9+9 (18.9 percent), 10+9 (7.5 percent), and 10+9+10 (7.5 percent). About 70 percent of the alleles with up to 40 repeats were linked to the DXS548/FRAXAC1 haplotype 7-3, the most commonly reported in normal populations. Four out of five intermediate alleles were in linkage with the two haplotypes most frequently associated to the FMR1 full mutation, 2-1 and 6-4. These four alleles showed long uninterrupted CGG repeats at the 3' end. The 9+9+22, 9+9+23 and 9+9+28 alleles were linked to the haplotype 2-1, and the 9+37 allele, to the haplotype 6-4. The pattern of AGG interspersion of these alleles and the associated haplotypes were in accordance with the two main pathways toward mutation previously proposed.