Fragile X syndrome, which is caused by expansion of a (CGG)n repeat in the FMR1 gene, occurs in approximately 1:3500 males and causes mental retardation/behavioral problems. Smaller (CGG)n repeat expansions in FMR1, premutations, are associated with premature ovarian failure and fragile X-associated tremor/ataxia syndrome. An FMR1-sizing assay is technically challenging because of high GC content of the (CGG)n repeat, the size limitations of conventional PCR, and a lack of reference materials available for test development/validation and routine quality control. The Centers for Disease Control and Prevention and the Association for Molecular Pathology, together with the genetic testing community, have addressed the need for characterized fragile X mutation reference materials by developing characterized DNA samples from 16 cell lines with repeat lengths representing important phenotypic classes and diagnostic cutoffs. The alleles in these materials were characterized by consensus analysis in nine clinical laboratories. The information generated from this study is available on the Centers for Disease Control and Prevention and Coriell Cell Repositories websites. DNA purified from these cell lines is available to the genetics community through the Coriell Cell Repositories. The public availability of these reference materials should help support accurate clinical fragile X syndrome testing.
Bibliographical noteFunding Information:
M.A.J. and C.S.R. are supported, in part, by Celera, Alameda, CA. The collection of biological samples and establishment of cell lines was supported , in part, by the National Institutes of Health [grants R01 HD29909 and National Center for Research Resources grant M01 RR00039 (S.L.S.) ]. The laboratories at ARUP Laboratories, Baylor College of Medicine, Emory University School of Medicine, Genzyme Genetics, Mayo Clinic, The Ohio State University, Oregon Health & Science University, Quest Diagnostics, University of Virginia Health Sciences Center, and Virginia Commonwealth University offer clinical fragile X testing on a fee for service basis.