The Principles of Clinical Cytogenetics - Extra Materials - Springer

Fragile X 497
Fig. 1. Appearance of FRAXA: (A) conventional stain (Giemsa) and (B) GTG-banded. The arrow indicates
the location of the fraX site.
Table 2
Fragile Sites on X Chromosome
Gene symbol Location Type Subtype a
FRAXA Xq27.3 Rare Folate-sensitive
FRAXB Xp22.31 Common Aphidicolin inducible
FRAXC Xq22.1 Common Aphidicolin inducible
FRAXD Xq27.2 Common Aphidicolin inducible
FRAXE Xq28 Rare Folate-sensitive
FRAXF Xq28 Rare Folate-sensitive
a Subtypes are discussed in Chapter 14.
FraX is not a chromosome abnormality. It is a chromosomal “marker” that allowed us to diagnose
fragile X syndrome in most cases while better techniques were being developed. Thus, the table
developed for chromosomal mosaicism (24) does not apply.
Cytogenetic Expression in Affected Males and Carrier Females
In affected males, fraX expression varied from less than 4% to 50%, with the low-expressing
males comprising a minority of the diagnosed cases. However, this group is the origin of the falsenegative
males diagnosable with molecular techniques. Why fraX does not express in more than 50%
of metaphases is still not known. Cytogenetic testing of carrier (heterozygous) females was even
more problematic. Among obligate carriers, only about 50% tested positive, and about one-third of
these carriers were clearly affected to some degree. In general, fraX expression was easier to demonstrate
(although lower than in males) in affected females than in those with normal intelligence.
Guidelines were established for interpretation of these data (8,9).