title: A five-year experience with fragile X testing. Setting laboratory standards of practice and a cost-effective protocol.
abstract: During the years 1990-1994, our center tested 652 patients, with a broad range of referral indications, for fragile X syndrome using either cytogenetic analysis alone (Protocol 1) or more recently, a combination of DNA analysis and routine karyotyping (protocol 2). The overall positive rate for fragile X was 3.1% with an incidence of other chromosomal abnormalities (OCAs) of 3.2%. Breakdown of cases using each testing protocol along with percent positives is: [table: see text] Use of Protocol 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 interpretation 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 appears to be unaffected by testing method used. The overall incidence of OCA of 3.2% underscores the value of routine karyotyping in this referral group and likely reflects the phenotypic variability of fragile X and its clinical overlap with other chromosomal abnormalities. We believe that a fragile X testing protocol combining routine karyotyping with definitive molecular technology represents the most cost-effective diagnostic approach to this clinically challenging patient population.
authors.affiliation: Baystate Medical Center, Springfield, MA 01199, USA.
authors.forename: T
authors.initials: T
authors.lastname: Marini
authors.forename: S
authors.initials: S
authors.lastname: Pflueger
authors.forename: A
authors.initials: A
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Naber
authors.forename: S
authors.initials: S
authors.lastname: Karpells
authors.forename: R
authors.initials: R
authors.lastname: Naeem
mesh_terms: D019411:Clinical Laboratory Techniques / Q000191:economics / Q000592:standards*; D003362:Cost-Benefit Analysis; D003582:Cytogenetics / Q000191:economics / Q000592:standards*; D004252:DNA Mutational Analysis; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007621:Karyotyping