Asymmetry of methylation with FMR-1 full mutation in two 45,X/46,XX mosaic females associated with normal intellect

• Published in: American journal of medical genetics Vol. 51; no. 4; p. 507
• Main Authors: Shapiro, L R, Simensen, R J, Wilmot, P L, Fisch, G S, Vibert, B K, Fenwick, R G, Tarleton, J, Phelan, M C
• Format: Journal Article
• Language: English
• Published: United States 15.07.1994
• Subjects: Adolescent; Adult; Aneuploidy; Dinucleoside Phosphates - metabolism; DNA - metabolism; Dosage Compensation, Genetic; Female; Fragile X Syndrome - complications; Fragile X Syndrome - genetics; Fragile X Syndrome - metabolism; Gene Dosage; Humans; Intelligence; Mosaicism; Mutation; Repetitive Sequences, Nucleic Acid; Turner Syndrome - complications
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320510443

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.