Noninvasive test for fragile X syndrome, using hair root analysis

Identification of the FMR1 gene and the repeat-amplification mechanism caus ing fragile X syndrome led to development of reliable DNA-based diagnostic methods, including Southern blot hybridization and PCR. Both methods are pe rformed on DNA isolated from peripheral blood cells and measure the repeat size in FMR1. Using an immunocytochemical technique on blood smears, we rec ently developed a novel test for identification of patients with fragile X syndrome. This method, also called "antibody test," uses monoclonal antibod ies against the FMR1 gene product (FMRP) and is based on absence of FMRP in patients' cells. Here we describe a new diagnostic test to identify male p atients with fragile X syndrome, on the basis of lack of FMRP in their hair roots. Expression of FMRP in hair roots was studied by use of an FMRP-spec ific antibody test, and the percentage of FMRP-expressing hair roots in con trols and in male fragile X patients was determined. Control individuals sh owed clear expression of FMRP in nearly every hair root, whereas male fragi le X patients lacked expression of FMRP in almost all their hair roots. Men tally retarded female patients with a full mutation showed FMRP expression in only some of their hair roots (<55%), and no overlap with normal female controls was observed. The advantages of this test are (1) plucking of hair follicles does no appreciable harm to the mentally retarded patient, (2) h airs can be sent in a simple envelope to a diagnostic center, and (3) the r esult of the test is available within 5 h of plucking. In addition, this te st enabled us to identify two fragile X patients who did not show the full mutation by analysis of DNA isolated from blood cells.