Postmortem examination of two fragile X brothers with an FMR1 full mutation

Large expansions of the CGG repeat in the 5' untranslated region of the FMR 1 gene are found in patients with the fragile X syndrome. Amplified CGG rep eats in FMR1 are unstable and show intergenerational increase from mother t o offspring. The exact timing of repeat amplification, however, is unknown, We have compared the extent of CGG expansion in various tissues of this de ceased fragile X patient, and found only limited variation in repeat expans ion. The repeat was fully methylated in all tissues examined. Therefore, no evidence for extensive mitotic expansion of the CGG repeat during fetal or postnatal life of a fragile X patient was found, in contrast to dynamic mu tations caused by CAG/CTG repeat expansion, Extensive pathological examination of this patient and his affected brother revealed no evidence for specific abnormalities relevant to fragile X synd rome; cerebellar hypoplasia, which has been reported in this disorder, was not evident in either patient. (C) 1999 Wiley-Liss, Inc.