ABSTRACT
The goal of the present two-step screening program [clinical selection followed by cytogenetic and molecular studies] is to identify affected males without adding too much load on the cytogenetic laboratory, and to inform their families about the diagnosis so that female relatives at risk can consider this information in their family planning and reproductive options. A total of 306 adult instituted males with mental retardation of unknown aetiology were screened for 10 clinical traits associated with the fragile X [fra[X]]syndrome, including physical features, behaviour and family history of mental retardation. Sixty-one [19.9%] males with a clinical score of > 5 were selected for cytogenetic and molecular analyses, thereby reducing the workload on the laboratory by 81.1%. Eleven patients [18%] were positive cytogenetically and confirmed by Southern blotting, so giving a 3.6% overall incidence of the fra[X] syndrome among the instituted males with mental retardation. The high clinical score increased the likelihood of a positive diagnosis [15% of the fragile X cases had a clinical score of 5-7, and 66% had a score of 8-10]. The expression of the fragile site at Xq27.3 ranged between 7%-34%, with a mean of 19.5%. Two patients had constitutional chromosomal abnormalities. This two-step screening program is cost effective and suitable for screening a large population at risk, with the advantage of reducing the workload on the laboratory without apparently impairing the ability to find patients with the fra[X] syndrome