FREQUENCY AND DISTRIBUTION OF CHROMOSOME FRAGILE SITES OR LESIONS IN MALES WITH MENTAL RETARDATION: A DESCRIPTIVE STUDY.

Abstract

Cytogenetic data using multiple cell culture conditions to induce different classes of fragile sites from males with mental retardation are limited. Thus, the frequency and distribution of chromosome fragile sites were assessed from peripheral blood lymphocytes of 165 institutionalized males (age range 18-86 years) with mental retardation screened for the fragile X syndrome but with no recognizable cause of their retardation. The cells were grown in folate-replete RPMI 1640 culture medium with bromodeoxyuridine (BrdU) or fluorodeoxyuridine (FUdR) and in folate-deficient Medium 199. A significantly higher number of fragile sites or lesions (1,118 vs. 301) was observed in cells grown in RPMI 1640 with FUdR than in Medium 199. Specifically, 6q26 and Xp22 sites were observed much more frequently in RPMI 1640 with FUdR than in Medium 199. Similarly, a significantly higher number of sites (612 vs. 332) was observed in cells from RPMI 1640 with BrdU than in Medium 199. Specifically, 3q27, 9q13 and 12q24 sites were observed more frequently in RMPI 1640 with BrdU. However the 3p14 site was observed more frequently in Medium 199. The fragile sites were non-random and unevenly distributed with the highest number of sites located on chromosome 3 (band 3p14) for both Medium 199 and RPMI 1640 with FUdR and for chromosome 16 (band 16q22) for RPMI 1640 with BrdU. Significantly more fragile sites were located on chromosomes 3 and 16 from cells grown in Medium 199; for chromosomes 3, 6, 7, and 16 for cells grown in RPMI 1640 with FUdR; and for chromosomes 4, 9, 10, and 16 for cells grown in RPMI 1640 with BrdU. In addition, the 301 fragile sites or lesions in cells grown in Medium 199 were found on 103 of a total of 306 chromosome bands: 1,118 sites on 203 bands from RPMI 1640 with FUdR and 612 sites on 145 bands from RPMI 1640 with BrdU. Eight sites each representing at least 2% of the total number of sites were found in cells grown in Medium 199; seven sites in cells from RPMI 1640 with FUdR and eight sites in cells from RPMI 1640 with BrdU. Only one site (3p14) was classified as a common site in >50% of the population while the other sites were polymorphic (in 1-50%) or rare (in <1%). The BrdU site at 9q13 was seen in 10% of males with mental retardation, accounted for 3.8% of all BrdU sites, and appears to be a newly reported or underreported site enhanced by BrdU.