Holden J J, Walker M, Chalifoux M, White B N
Department of Psychiatry, Queen's University, Kingston, Ontario, Canada.
Am J Med Genet. 1996 Aug 9;64(2):424-7. doi: 10.1002/(SICI)1096-8628(19960809)64:2<424::AID-AJMG38>3.0.CO;2-F.
FRAXF, the third X-chromosomal fragile site to be cloned, has been shown to harbour a polymorphic compound triplet array: (GCCGTC)n (GCC)n. Expansion and methylation of the GCC-repeat and the neighbouring CpG-rich region result in chromosomal fragility. DNAs from 500 anonymous consecutive newborn males were examined to determine the incidence of various repeat numbers. The range of repeats was from 10-38, with the most common alleles having 14 (52.7%), 12 (16.6%), 21 (9.0%), and 22 (5.2%) triplets. Based on the distribution of repeat numbers, we suggest that the 21-repeat allele resulted from hairpin formation involving 7 GCC-repeats in a 14-repeat allele, accompanied by polymerase slippage. Examination of dinucleotide repeats near the FRAXF repeat will be important in testing this hypothesis. Since the clinical phenotype, if any, of FRAXF is unknown, this database will also be valuable for comparisons with repeat numbers in individuals from special populations.
