Chromosome lesions which could be interpreted as "fragile sites" on the distal end of Xq

Abstract

Chromosome lesions which could be interpreted as "fragile sites" on the distal end of the long arm of the X chromosome were identified during a cytogenetic study of 160 mentally retarded adult males with no apparent cause of their mental retardation and one normal adult female with a family history of fra (X) syndrome. Peripheral blood samples were cultured in either M199 or RPMI 1640 medium with FUdR or BrdU. Metaphases were examined for chromosome lesions or fragile sites on the distal end of Xq and 3 distinct sites were observed: Xq26, Xq27.2, and Xq27.3. Other chromosome lesions at Xq28 were observed and interpreted as nonspecific telomeric structural changes. Chromosome lesions were observed in cells from 14 of the 161 individuals. These included: 5 patients with an Xq26 site, 2 with the recently reported Xq27.2 site, 4 with the Xq27.3 site (characteristic of the fra (X) syndrome), 2 with nonspecific telomeric structural changes, and one individual with 2 lesions (a nonspecific telomeric structural change and an Xq26 site). Additional research is necessary to determine the frequency and clinical significance, if any, of lesions occurring in this region of the X chromosome and to distinguish among heritable fragile sites, constitutive fragile sites, and nonspecific telomeric structural changes.

Fig. 1

Collection of X chromosomes showing lesions at Xq26, Xq27.2, Xq27.3, and nonspecific telomeric structural changes (TSC). The idiogram (400 band level) shows the location of the bands for the X chromosome. The break at Xq26 clearly occurs proximal to the Giemsa-positive Xq27 band. The Xq27.2 site is proximal to and distinct from the Xq27.3 band observed in fra (X) syndrome patients. A nonspecific telomeric structural change, atypical in appearance for a fragile site, is located at Xq28 or qterminus (the Xp22 fragile site can also be seen in this X chromosome) [top]. X chromosome idiogram (850 band level) and a representative prometaphase X chromosome from a patient with fra (X) syndrome banded with the GTG method showing the location of the Xq27.3 fragile site [bottom].