Monozygotic twin brothers with the fragile X syndrome: different CGG repeats and different mental capacities
- A T J M Helderman-van den Endena,
- P D Maaswinkel-Mooijb,
- E Hoogendoorna,c,
- R Willemsend,
- J A Maat-Kievita,d,
- M Losekoota,c,
- B A Oostrad
- aDepartment of Clinical Genetics, K5-R, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands, bDepartment of Paediatrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands, cMGC Department of Human Genetics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands, dMGC Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
- Dr Helderman-van den Enden.
- Received 8 May 1998
- Revised 4 August 1998
Abstract
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.
