THE NUMBER OF CGG REPEATS OF THE FMR1 LOCUS IN PREMUTATED AND FULLY MUTATED HETEROZYGOTES AND THEIR OFFSPRING - IMPLICATIONS FOR THE ORIGINOF MOSAICISM
Rc. Mingroninetto et al., THE NUMBER OF CGG REPEATS OF THE FMR1 LOCUS IN PREMUTATED AND FULLY MUTATED HETEROZYGOTES AND THEIR OFFSPRING - IMPLICATIONS FOR THE ORIGINOF MOSAICISM, American journal of medical genetics, 64(2), 1996, pp. 270-273
The size of the CGG repeat of the FMR1 gene was investigated with prob
e StB12.3 in 154 transmissions to the offspring of heterozygotes for t
he premutation and the full mutation. Among the 135 offspring of premu
tated heterozygotes there were three decreases in size of the repeats:
in two of these cases a full mutation was present along with the decr
eased premutation, and in a third mosaic (46,fra(X)(q27.3),Y), a norma
l allele was observed. In the 19 offspring of fully mutated females wi
th no detected mosaicism, there were three mosaics and three individua
ls who had full mutations that included a number of repeats smaller th
an those present in their mothers. Among the 32 offspring who received
a premutation from their premutated mothers, 27 alleles were increase
d in size and 5 remained unaltered. Among 11 mosaic offspring of premu
tated mothers, the premutation increased in 4, decreased in 3, and was
unchanged in 4. In contrast to the trend of an increasing premutation
size in the non-mosaic offspring, the premutation present in mosaics
can be smaller, larger, or of unaltered size with approximately equal
frequencies. These data suggest that the premutations present in mosai
cs result from mitotic instability of the inherited full mutations. Th
is is further supported by the finding of a mosaic male with a normal
sized allele. (C) 1996 Wiley-Liss, Inc.