Genotype, molecular phenotype, and cognitive phenotype: correlations in XXXX .

@entity10308 @entity2100
The study of the neurobehavioral consequences of mutations of @entity10308 , the gene responsible for @entity2100 ( @entity2100 ), has been based largely on correlations between mutation patterns and cognitive profile. Following the characterization of @entity10308 , the @entity10308 gene product, preliminary correlations between @entity10308 levels, and neurologic phenotype have been established. However, most of these investigations have focused on individuals at both ends of the genetic and cognitive spectra of @entity2100 , subjects with normal or premutation (PM) alleles or males with the @entity10308 full mutation (FM). The present study is designed to characterize @entity10308 expression and to correlate it with IQ, in a sample representing a wide spectrum of @entity10308 mutations. For this purpose we developed a highly sensitive immunoblotting assay using peripheral leukocytes. Three distinct patterns of @entity10308 immunoreactivity (-ir) emerged. Individuals with normal (n = 28) and PM (n = 8) alleles as well as most females with the FM (n = 14) showed the highest levels with multiple approximately 70-80 kDa @entity10308 -ir bands. Males with the FM (n = 10) demonstrated only a 70 kDa @entity10308 -ir band, and had significantly lower levels when compared with any previous groups. Males with mosaicism and three of 14 females with FM displayed a doublet with equal amounts of the highest and lowest molecular weight @entity10308 -ir bands. Multiple regression models that adjust for the effect of parental IQ indicated that both activation ratio and @entity10308 -ir are significantly correlated to subject IQ. We conclude that @entity10308 -ir offers promise as an indicator of the impact of @entity10308 mutations upon neurologic function. Furthermore, our unexpected finding of @entity10308 -ir in all males with FM suggests that most of them are not transcriptionally silent.
