The identification of a third fragile site, FRAXF, in Xq27--q28 distal to both FRAXA and FRAXE.
FRAXA is unique amongst fragile sites in that it is intimately involved with a specific clinical phenotype, the fragile X syndrome. Whilst the majority of fragile X individuals have been found to have a characteristic mutation in the FMR1 gene, a small proportion of individuals exhibiting fragility have no such mutation. Investigation of the site of chromosome fragility in these FMR1 mutation negative, fragile X site positive individuals, has identified a second site of fragility, FRAXE. However, the presence of FRAXE has not explained all such cases. Here we describe a fragile X site positive, FMR1 mutation negative family, in which chromosome fragility is not due to the FRAXA or FRAXE but is due to a third site designated FRAXF. Using fluorescent in situ hybridisation (FISH) this site is shown to lie over 1Mb distal to FRAXA. The identification of a third fragile site in this small region of the X chromosome provides an opportunity to extend our studies of the molecular nature of chromosome fragility.
Hirst
M C
MC
Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Barnicoat
A
A
Flynn
G
G
Wang
Q
Q
Daker
M
M
Buckle
V J
VJ
Davies
K E
KE
Bobrow
M
M
D000293:Adolescent; D000328:Adult; D002843:Chromatin / Q000648:ultrastructure; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D010375:Pedigree; D014960:X Chromosome / Q000648:ultrastructure*
D002843:Chromatin; D005819:Genetic Markers