OBJECTIVES: To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes. METHODS: We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education. RESULTS: We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity. CONCLUSIONS: The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.
OBJECTIVES: To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes. METHODS: We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education. RESULTS: We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity. CONCLUSIONS: The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.
Authors: Cesa Scaglione; Andrea Ginestroni; Alessandra Vella; Maria Teresa Dotti; Riccardo Della Nave; Giovanni Rizzo; Maria Teresa De Cristofaro; Nicola De Stefano; Silvia Piacentini; Paolo Martinelli; Mario Mascalchi Journal: J Neurol Date: 2007-12-19 Impact factor: 4.849
Authors: James A Bourgeois; Sarah M Coffey; Susan M Rivera; David Hessl; Louise W Gane; Flora Tassone; Claudia Greco; Brenda Finucane; Lawrence Nelson; Elizabeth Berry-Kravis; Jim Grigsby; Paul J Hagerman; Randi J Hagerman Journal: J Clin Psychiatry Date: 2009-05-05 Impact factor: 4.384
Authors: Joan A O'Keefe; Erin Robertson-Dick; Emily J Dunn; Yan Li; Youping Deng; Amber N Fiutko; Elizabeth Berry-Kravis; Deborah A Hall Journal: Cerebellum Date: 2015-12 Impact factor: 3.847
Authors: P E Adams; J S Adams; D V Nguyen; D Hessl; J A Brunberg; F Tassone; W Zhang; K Koldewyn; S M Rivera; J Grigsby; L Zhang; C Decarli; P J Hagerman; R J Hagerman Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2010-04-05 Impact factor: 3.568