Monozygotic twin brothers with the fragile X syndrome: different CGG repeats and different mental capacities.
Little is known about the mechanism of CGG instability and the time frame of instability early in embryonic development in the fragile X syndrome. Discordant monozygotic twin brothers with the fragile X syndrome could give us insight into the time frame of the instability. We describe monochorionic diamniotic twin brothers with the fragile X syndrome who had different CGG repeats and different mental capacities, whereas the normal mother had a premutation. The more retarded brother had a full mutation in all his cells and no FMR-1 protein expression in lymphocytes, whereas the less retarded brother had 50%/50% mosaicism for a premutation and full mutation and FMR-1 protein expression in 26% of his lymphocytes. The differences in repeat size could have arisen either before or after the time of splitting. The time of splitting in this type of twin is around day 6-7. Given the high percentage of mosaicism, we hypothesise that the instability started before the time of splitting at day 6-7.
Helderman-van den Enden
A T
AT
Department of Clinical Genetics, Leiden University Medical Centre, The Netherlands.
Maaswinkel-Mooij
P D
PD
Hoogendoorn
E
E
Willemsen
R
R
Maat-Kievit
J A
JA
Losekoot
M
M
Oostra
B A
BA
D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D006801:Humans; D008297:Male; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016601:RNA-Binding Proteins; D018911:Trinucleotide Repeats; D014430:Twins, Monozygotic / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human