GENOTYPE-PHENOTYPE RELATIONSHIP IN FEMALE CARRIERS OF THE PREMUTATIONAND FULL MUTATION OF FMR-1

The present French-German cooperative study focuses on the genotype-ph enotype relationship of mutations of the FMR-1 gene and psychiatric co nditions in mothers with a full mutation in the FMR-1 gene of fra-X ch ildren (n = 13), mothers with a premutation in the FMR-1 gene of fra-X children (n = 61), as well as premutated siblings of these mothers wi thout affected children (n = 17) and two non-mutated control groups: ( 1) siblings of these mothers with normal CGG repeat (n = 18); and (2) mothers of non-fra-X autistic children (n = 42). Mothers with a full m utation in the FMR-1 gene and mothers with a premutation in the FMR-1 gene did not differ in the frequency of any axis I disorder; however, both groups were diagnosed with social phobia more often than the cont rol group of mothers of autistic children. Moreover, mothers with a pr emutation in the FMR-1 gene of fra-X children and their siblings with the premutation (without affected offspring) revealed a similar freque ncy of social phobia. Furthermore avoidant personality disorder was mo re common in groups of carriers of the full premutation than in siblin gs without mutation or than the control group of mothers with autistic children. On the basis of our data, we therefore suggest that social avoidance (expressed as social phobia or avoidant personality disorder ) has been underestimated in previous studies of carriers with the FMR -1 full mutation or premutation. Comorbidity of axis I and axis II psy chiatric diagnoses was mainly restricted to the group of carriers of t he full mutation and carriers of the premutation of FMR-1. Correlation s between size of CGG repeat and IQ as well as CGG and age of onset of axis I diagnosis were non-significant. IQ of subjects had no impact o n presence or absence of axis I and/or axis II diagnoses (C) 1998 Else vier Science Ireland Ltd. All rights reserved.