Published online before print December 28, 2007

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Journal of Molecular Diagnostics 2008, Vol. 10, No. 1
Copyright © 2008 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2008.070105

Special Article

Consensus Characterization of 16 FMR1 Reference Materials: A Consortium Study

Jean Amos Wilson^*, Victoria M. Pratt, Amit Phansalkar, Kasinathan Muralidharan, W. Edward Highsmith, Jr^¶, Jeanne C. Beck^||, Scott Bridgeman^**, Ebony M. Courtney, Lidia Epp, Andrea Ferreira-Gonzalez, Nick L. Hjelm, Leonard M. Holtegaard^¶, Mohamed A. Jama, John P. Jakupciak, Monique A. Johnson, Paul Labrousse^||||, Elaine Lyon^||||, Thomas W. Prior^**, C. Sue Richards, Kristy L. Richie, Benjamin B. Roa^***, Elizabeth M. Rohlfs^¶¶, Tina Sellers^||, Stephanie L. Sherman, Karen A. Siegrist, Lawrence M. Silverman, Joanna Wiszniewska^***, Lisa V. Kalman^|||||| and the Fragile Xperts Working Group of the Association for Molecular Pathology Clinical Practice Committee

From Sequenom, *San Diego, California; Quest Diagnostics, Nichols Institute, Chantilly, Virginia; ARUP Laboratories, Salt Lake City, Utah; Emory University School of Medicine, Atlanta, Georgia; Mayo Clinic, ^¶Rochester Minnesota; Coriell Institute for Medical Research, ^||Camden, New Jersey; The Ohio State University, **Columbus Ohio; Virginia Commonwealth University, Richmond, Virginia; National Institute of Standards and Technology, Gaithersburg, Maryland; Oregon Health & Science University, Portland, Oregon; Genzyme Genetics, ^¶¶Westborough, Massachusetts; University of Utah, ^||||Salt Lake City Utah; Baylor College of Medicine, ***Houston, Texas; University of Virginia Health Sciences Center, Charlottesville, Virginia; Centers for Disease Control and Prevention, Atlanta, Georgia

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.