UNEXPECTED INHERITANCE OF THE (CGG)(N) TRINUCLEOTIDE EXPANSION IN A FRAGILE-X SYNDROME FAMILY

The fragile X syndrome is the most frequent cause of inherited mental retardation. CGG repeat alleles are usually classified as normal, prem utation, or full mutation based on the length of this triplet in the 5 ' untranslated region of the FMR1 gene. The pattern of inheritance fol lows a two-stage intergenerational process in which the premutation ev olves into the full mutation. Some reverse mutations have been describ ed, but they appear to be very rare. We describe a family in which a m other of two affected males herself carried a full mutation. Surprisin gly, her clinically normal daughter, initially considered to be a carr ier by linkage analysis, carried a very short premutation. Findings fr om our family study corroborate the hypothesis that the expansion duri ng female transmission could be a postzygotic event and raise the prob lem of mosaicism.