Triplet (CGG) expansion at the FMR-1 locus: Fragile-X Syndrome

    At the FMR-1 locus on the X chromosome, most individuals have from 6 ~ 54 copies of a CGG repeat. Slipped-mismatch repair in the female germline gradually increases the number of CGG repeats in some families.  Normally-transmitting males & their daughters are phenotypically unaffected. In these daughters, unequal crossing-over between X chromosomes with a high CGG copy number further increases the copy number. At a threshold of ~200 copies, affected offspring will show the Fragile-X Syndrome of mental retardation.  The phenotype is less common in females, where the alternative X chromosome with a low number of CGG copies masks expression.

    The repeat region creates a "satellite" at the end of the long arm of the  X-chromosome that is subject to breakage, and which is cytologically detectable as a "fragile X" chromosome.

Figure © 2000 by Griffiths et al. ; text © 2014 by Steven M. Carr