Fully mutated and gray-zone FRAXA alleles in Brazilian mentally retarded boys

We used a non-isotopic polymerase chain reaction (PCR) technique for fragil e X syndrome diagnosis to screen 256 mentally retarded boys who were select ed randomly from special schools. Patients identified as pre- or full-mutat ion carriers were further investigated by Southern blot analysis with the S tB12.3 probe. The PCR-based test identified five boys with the expanded all ele and 17 other patients as carriers of either premutated or gray-zone all eles, The full mutation was confirmed in four cases after Southern blotting and a fifth patient carried a normal allele, Of the 17 patients identified with a premutation allele by PCR, one individual was diagnosed as mosaic b y Southern blotting, 12 individuals displayed fragments of 2.90 kb or 2.85 kb, and the remaining four individuals showed apparently normal-sized fragm ents. However, sizing of these 16 alleles by further PCR analysis showed th em to be in the gray-zone range (40-60 repeats). Therefore, the frequency o f the full mutation in this cohort of mentally retarded boys was close to 2 % (5/256), The prevalence of gray-zone alleles among those mentally impaire d boys who did not carry the full mutation was 6.4% (16/251) and, although more than twice the prevalence of these alleles among a cohort of unaffecte d Brazilian males 2.8% (7/251), the difference did not reach statistical si gnificance. (C) 1999 Wiley-Liss, Inc.