ELECTRONIC LETTER

Intranuclear inclusions in neural cells with premutation alleles in fragile X associated tremor/ataxia syndrome

F Tassone¹, R J Hagerman², D Garcia-Arocena¹, E W Khandjian³, C M Greco⁴, P J Hagerman¹

¹ Department of Biological Chemistry, School of Medicine, University of California Davis, CA, USA
² M.I.N.D. Institute and Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, USA
³ Department of Medical Biology, Laval University, Quebec, Canada
⁴ Department of Pathology, University of California Davis Medical Center, Sacramento, CA, USA

Correspondence to:
Correspondence to:
F Tassone
Department of Biological Chemistry, UC Davis School of Medicine, One Shields Avenue, Davis, CA 95616, USA; ftassone@ucdavis.edu

Keywords: neurodegeneration; neurodevelopment; CGG trinucleotide repeat; FMR1 mRNA; FMRP; somatic stability

The first 150 words of the full text of this article appear below.

Fragile X syndrome is generally considered to be a non-progressive neurodevelopmental disorder in which carriers of premutation alleles (~55 to 200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are largely unaffected. However, we have recently identified a new syndrome among male carriers, characterised by tremor and/or ataxia, cognitive deficits, parkinsonism, and autonomic dysfunction.^1,5,6,8,10 Neuroradiological findings include moderate to severe cortical atrophy (cerebral and cerebellar cortical volume loss) and characteristic hyperintensities on T2-weighted MR imaging of the deep cerebellar white matter and middle cerebellar peduncles.^2,8 The disorder, termed fragile X associated tremor/ataxia syndrome,⁸ has been observed thus far almost exclusively in older adult male premutation carriers of more than 50 years of age.

Eosinophilic intranuclear inclusions are broadly distributed in both neurones and astrocytes throughout the cerebrum and brain stem of all persons with fragile X associated tremor/ataxia syndrome (FXTAS) examined to date (8/8),^5,7 with the greatest . . . [Full text of this article]

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