Human Molecular Genetics, Vol 6, 435-441, Copyright © 1997 by Oxford University Press
J Gecz, BA Oostra, A Hockey, P Carbonell, G Turner, EA Haan, GR Sutherland and JC Mulley
Normal individuals express the two alternative transcripts, FMR2 and Ox19,
from the FRAXE-associated CpG island. Molecular analysis of the Ox19
transcript suggests that it is a truncated isoform of the FMR2 gene with an
alternative 3' end. Both isoforms showed a similar pattern of expression,
with the Ox19 isoform expressed at a much lower level. Fibroblasts,
chorionic villi and hair roots showed the highest level of FMR2 expression,
whole blood cells and amniocytes showed very low expression, and the
transcript was not detected in lymphoblasts. Fibroblasts of 11 individuals
from seven families segregating FRAXE were assayed for FMR2 expression and
FRAXE CpG island methylation. A man with an unmethylated expansion of 0.6
kb expressed FMR2 and represents a pre-mutation carrier. All chromosomes
with FRAXE CCG expansions of 0.8 kb or greater were fully methylated and
did not express the FMR2 gene, analogous to the mechanism of silencing the
FMR1 gene in carriers of the FRAXA full mutation. The boundary between
FRAXE pre-mutation and FRAXE full mutation is between 0.7 and 0.8 kb. Two
men with absence of FMR2 expression in fibroblasts were not mentally
impaired, suggesting that IQ in some men with FRAXE full mutation may
remain within the normal range. Although molecular tools to study FRAXE
non-specific mental retardation are now available, further psychometric and
molecular studies are needed to characterize the effect of the FRAXE full
mutation for the purpose of genetic counselling.
ARTICLES
FMR2 expression in families with FRAXE mental retardation
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, Australia.
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