MOLECULAR CLINICAL CORRELATIONS IN FEMALES WITH FRAGILE-X/

Females who are affected by fragile X syndrome (FXS) can have signific ant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypi c areas relates to molecular parameters including CGG repeat length an d activation ratio (the proportion of normal FMP1 alleles on the activ e X chromosome). Three groups of females were studied: 35 women who gr ew up in a fragile X family but do not carry an FMR1 mutation, 92 wome n with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significa nt correlations were seen between schizotypal traits and full scale IQ . The Lie scale was significantly correlated with the physical finding s index. The activation ratio correlated significantly with the measur e of executive function (r = .50, P = .01). There was a trend toward c orrelations of activation ratio with the physical index score, outer e ar prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .01). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in d etermining the degree of cognitive and physical phenotypic involvement . (C) 1996 Wiley-Liss, Inc.