Reliability of diagnostic assessment of normal and premutation status in the fragile X syndrome using DNA testing

✍ Scribed by Fisch, Gene S. ;Nelson, David L. ;Snow, Karen ;Thibodeau, Stephen N. ;Chalifoux, Maryse ;Holden, Jeanette J. A.

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 534 KB
• Volume: 51
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320510409

✦ Synopsis

Until recently, fragile X [fra(X)] syndrome was diagnosed by cytogenetic techniques and/or linkage analysis. Investigation of the mutation at the molecular level has shown that amplification of a polymorphic trinucleotide repeat (CGG) is diagnostic of this syndrome. Fu et al. [1991] observed that between 6-54 copies of the repeat were associated with alleles found in the general population, whereas 50-200 copies were associated with the premutation. In general, differences in copy number between the normal and premutated states are sufficiently large so that the probability of misclassification is, for all practical purposes? zero. However, there is a grey area in which members from both populations overlap. The purpose of our study was to determine the probability of misclassifying an individual from either the general or premutation population. DNA obtained from the general population and transmitting fra(X) females were analyzed from 3 centers in North