FMR1 CGG-repeat instability in single sperm and lymphocytes of fragile-X premutation males

Abstract

To determine the meiotic instability of the CGG-triplet repeat in the fragile-X gene, FMR1, we examined the size of the repeat in single sperm from four premutation males. The males had CGG-repeat sizes of 68, 75, 78, and 100, as determined in peripheral blood samples. All samples showed a broad range of variations, with expansions more common than contractions. Examination of single lymphocytes indicated that somatic cells were relatively more stable than sperm. Surprisingly, the repeats in sperm from the 75- and 78-repeat males had very different size ranges and distribution patterns despite the similarity of the repeat size and AGG interruption in their somatic cells. These results suggest that cis or trans factors may have a role in male germline repeat instability.