Fragile X Syndrome Full Mutation Females at Increased Risk for Mosaic Turner Syndrome: Fragile X Leads to Chromosome Loss

Fragile X Syndrome, the most common form of inherited mental retardation, is characterized by autistic behavior and mild to severe learning disabilities. The disease is caused by the expansion of a trinucleotide repeat located on the FMR1 (Fragile X Mental Retardation) gene located on the Xchromosome. Since the early 1990s, 348 prenatal female samples have been analyzed for Fragile X Syndrome at the NYS Institute of Basic Research in Developmental Disabilities. Of the 94 Fragile X affected females found, five of these cases were also determined to be afflicted with an extremely rare (1 in 20,000-30,000) disease, known as mosaic Turner Syndrome. Five cases of Fragile X/Mosaic Turner affected females discovered in such a small sample size contradict the diseases’ low prevalence. This led to the hypothesis that there is a connection between Fragile X Syndrome and Turner Syndrome. In order to strengthen this hypothesis, we assessed the origin of the lost chromosome, and aimed to provide a mechanism by which the chromosome is lost. We believed the maternal Fragile X chromosome was being lost in these cases. Using the DXS451 and androgen receptor polymorphisms in polymerase chain reactions (PCR) and capillary electrophoresis, analysis of the five affected females and their parents allowed us to size the alleles and to identify the origin of parental chromosome loss. Two long term lymphoblastoid (LTL) cell lines of different full mutation females were also harvested for observations of chromosome loss over time. After allele sizing, 4 of the 5 Fragile X/mosaic Turner cases and 1 of the 2 LTL cell lines in our study depicted loss of the mutated maternal chromosome. These results suggest that the LTL cell lines can be used as a reliable technique for modeling parental sex chromosome loss over time. More importantly, however, these results suggest that a Fragile X chromosome may have a predisposition to be lost in somatic cells.