title: Genotype-phenotype relationship in female carriers of the premutation and full mutation of FMR-1.
abstract: The present French-German cooperative study focuses on the genotype-phenotype relationship of mutations of the FMR-1 gene and psychiatric conditions in mothers with a full mutation in the FMR-1 gene of fra-X children (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 without 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 mutation 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 control group of mothers of autistic children. Moreover, mothers with a premutation in the FMR-1 gene of fra-X children and their siblings with the premutation (without affected offspring) revealed a similar frequency of social phobia. Furthermore avoidant personality disorder was more common in groups of carriers of the full premutation than in siblings 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 psychiatric diagnoses was mainly restricted to the group of carriers of the full mutation and carriers of the premutation of FMR-1. Correlations 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 on presence or absence of axis I and/or axis II diagnoses.
authors.affiliation: Department of Psychiatry, University of Bonn, Germany. franke@uni-bonn.de
authors.forename: P
authors.initials: P
authors.lastname: Franke
authors.forename: M
authors.initials: M
authors.lastname: Leboyer
authors.forename: M
authors.initials: M
authors.lastname: Gänsicke
authors.forename: O
authors.initials: O
authors.lastname: Weiffenbach
authors.forename: V
authors.initials: V
authors.lastname: Biancalana
authors.forename: P
authors.initials: P
authors.lastname: Cornillet-Lefebre
authors.forename: M F
authors.initials: MF
authors.lastname: Croquette
authors.forename: U
authors.initials: U
authors.lastname: Froster
authors.forename: S G
authors.initials: SG
authors.lastname: Schwab
authors.forename: F
authors.initials: F
authors.lastname: Poustka
authors.forename: M
authors.initials: M
authors.lastname: Hautzinger
authors.forename: W
authors.initials: W
authors.lastname: Maier
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D019964:Mood Disorders / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D010554:Personality Disorders / Q000235:genetics; D010641:Phenotype; D011618:Psychotic Disorders / Q000235:genetics; D016601:RNA-Binding Proteins
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human