Asymmetry of methylation with FMR-1 full mutation in two 45,X/46,XX mosaic females associated with normal intellect.
The full FMR-1 mutation is known to cause the fragile X syndrome [Fra(X)], but variable expression in females, including normal to deficient intellect, may be related to random X-inactivation (lyonization). We have evaluated 2 mosaic 45,X/46,XX females who are cytogenetically fra(X) positive, have an FMR-1 full mutation, and are of normal intellect. There were 50% fra(X) chromosomes in the 45,X cells of one of the females; this has not been reported previously. In both patients, there was a strong asymmetry of FMR-1 methylation with the normal allele being totally or 90% unmethylated and the mutant allele being similarly methylated. Thus, the apparent selective inactivation of the full mutant FMR-1 allele appears to have resulted in limited expression with normal intellect. The presence of the fra(X) chromosome in 45,X cells is unique; however, there may be no relationship to the asymmetric inactivation of the mutant allele which could be due to chance or a mechanism yet to be delineated.
Shapiro
L R
LR
Department of Pediatrics, New York Medical College, Valhalla.
Simensen
R J
RJ
Wilmot
P L
PL
Fisch
G S
GS
Vibert
B K
BK
Fenwick
R G
RG
Tarleton
J
J
Phelan
M C
MC
D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D004247:DNA / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D005260:Female; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D006801:Humans; D007360:Intelligence; D009030:Mosaicism; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D014424:Turner Syndrome / Q000150:complications
D004247:DNA; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide