A 5-YEAR EXPERIENCE WITH FRAGILE-X TESTING - SETTING LABORATORY STANDARDS OF PRACTICE AND A COST-EFFECTIVE PROTOCOL

During the years 1990-1994, our center tested 652 patients, with a bro ad range of referral indications, for fragile X syndrome using either cytogenetic analysis alone (Protocol 1) or, more recently, a combinati on of DNA analysis and routine karyotyping (Protocol 2). The overall p ositive rate for fragile X was 3.1% with an incidence of other chromos omal abnormalities (OCAs) of 3.2%. Breakdown of cases using each testi ng protocol along with percent positives is: [GRAPHICS] Use of Protoco l 2 yielded only definitive fragile X results, while more than half of the ''positives'' using Protocol 1 were equivocal. Historically this has been problematic for both the laboratory and physician since inter pretation is often dependent on an equally equivocal clinical picture. Protocol 2 eliminates these diagnostic dilemmas without compromising detection of other chromosomal abnormalities, the incidence of which a ppears to be unaffected by testing method used. The overall incidence of OCA of 3.2% underscores the value of routine karyotyping in this re ferral group and likely reflects the phenotypic variability of fragile X and its clinical overlap with other chromosomal abnormalities. We b elieve that a fragile X testing protocol combining routine karyotyping with definitive molecular technology represents the most cost-effecti ve diagnostic approach to this clinically challenging patient populati on.