Characterisation and expression of a large, 13.7 kb FMR2 isoform.

FMR2 is the gene associated with FRAXE fragile site non-specific mental ret ardation (FRAXE MRX), Previously a male patient was identified with develop mental delay and speech problems who had a deletion within intron 3 of FMR2 . No known FMR2 exonic sequences were missing in this patient. Detailed nor thern blot analysis revealed existence of a new large isoform of FRM2 in fo etal brain, This isoform was characterised and found to be due entirely to an addition of an extra 4.9 kb of the 3' UTR to the previously characterise d 8.755 kb FMR2 transcript. This excluded involvement of the large FMR2 iso form in the MRX phenotype of three individuals now known to have the same d eletion of intron 3 FMR2 sequences. Expression studies on the new 13.7 kb F MR2 isoform show that it is expressed predominantly in foetal brain and adu lt pituitary gland, whilst the expression of the shorter previously charact erised 8.755 kb isoform is broader, including testis, thymus and placenta. Possible consequences of the alternative processing and expression of FMR2 for the molecular pathology of FRAXE MRX are discussed.