Molecular-intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene.
Several mechanisms can explain the occurrence of full-mutation fragile X males with an IQ level above -2 SD below mean, also called "high-functioning fragile X males." Incomplete methylation of the CpG island at the 5' end of the FMR1 gene is one of these mechanisms. The present study describes the physical and behavior phenotypes in 7 fragile X boys with CGG repeat insertions in the FMR1 gene between 600-2,400 base pairs. The degree of methylation at the FMR1-associated CpG island ranges in peripheral blood lymphocytes from 0-95%. Subjects with a low degree of methylation at this site have mild or absent physical characteristics of the fragile X syndrome, while subjects with a high degree of methylation at this site have more severe physical characteristics. In this range of CGG repeat insertion (600-2,400 base pairs), the degree of methylation at the FMR1-associated CpG island is a good predictor of intelligence, while CGG repeat insertion length is not.
Steyaert
J
J
Center of Clinical Genetics, Maastricht, The Netherlands.
Borghgraef
M
M
Legius
E
E
Fryns
J P
JP
D000293:Adolescent; D002648:Child; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D004251:DNA Transposable Elements; D015226:Dinucleoside Phosphates / Q000032:analysis; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000523:psychology*; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008214:Lymphocytes; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D016601:RNA-Binding Proteins; D018911:Trinucleotide Repeats
D004247:DNA; D004251:DNA Transposable Elements; D015226:Dinucleoside Phosphates; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C015772:CpG dinucleotide