MOSAICISM FOR THE FMR1 GENE INFLUENCES ADAPTIVE SKILLS DEVELOPMENT INFRAGILE X-AFFECTED MALES

Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associ ated with expanded trinucleotide repeats, Previously, we found that ab out 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher leve ls of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results , In the present study, the cross-sectional development of communicati on, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two varia bles: age and the presence or absence of mosaicism, The rate of adapti ve skills development was 2-4 times as great in mosaic cases as in ful l mutation cases, There was also a trend for cases with autism to be m ore prevalent in the full-mutation group. These results have implicati ons for prognosis, for the utility of gene or protein replacement ther apies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome, (C) 1996 Wiley-Liss, Inc.