Phenotypic variation and FMRP levels in fragile X

Abstract

Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier findings. The previously unpublished results obtained, using standard procedures of regression and correlations, showed highly significant associations in males between FMRP levels and the Wechsler summary and subtest scores and in females between these levels and the full-scale intelligence quotient (FSIQ), verbal and performance IQ, and some Wechsler subtest scores. The published results based on data from 144 extended families with fragile X, recruited from Australia and the United States within a collaborative NIH-supported project, were obtained using robust modification of maximum likelihood in pedigrees. The results indicated that processing speed, short-term memory, and the ability to control attention, especially in the context of regulating goal-directed behavior, may be primarily affected by the FMRP depletion. The effect of this depletion on physical phenotype was also demonstrated, especially on body and head height and extensibility of finger joints. It is recommended that further studies should rely on more accurate measures of FMRP levels, and use of larger samples, to overcome extensive variability in the data.

The expression and assessment of emotions and internal states in individuals with severe or profound intellectual disabilities

“…Fragile-X syndrome is the most common inherited cause of intellectual disability with a current prevalence of one in 4000-6000 live births (Turner, Webb, Wake, & Robinson, 1996). There are differences in the phenotype between males and females because of the association with the X chromosome (Loesch, Huggins, & Hagerman, 2004), with males…”

Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome

“…However, given the low numbers of individuals included in these groups, and the large age range of the individuals, these data should be treated cautiously. In a larger cross-sectional study, FMRP levels accounted for 52% of the variance in IQ scores in 68 males and approximately 12% of the variance in the IQ scores of 56 females (Loesch et al 2004). However, several methodological problems also limit the conclusions that can be drawn from this study.…”

“…Some investigators (Loesch et al 2004;Tassone et al 1999a, b), but not others (Skinner et al 2005), have reported a correlation between FMRP levels and intellectual functioning. Further, the association between FMRP and intellectual functioning appears to differ according to gender and methylation status.…”

An analysis of challenging behavior, comorbid psychopathology, and Attention-Deficit/Hyperactivity Disorder in Fragile X Syndrome

“…The FMR1 full mutation is associated with an 85% incidence of ID in males and 25% incidence of ID in females (Hagerman & Hagerman, 2002;Loesch, Huggins, & Hagerman, 2004). A number of physical features associated with the full mutation are observed, especially in males.…”