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Abnormal Nerve Conduction Features in Fragile X Premutation Carriers
Kultida Soontarapornchai, MD;
Ricardo Maselli, MD;
Grace Fenton-Farrell;
Flora Tassone, PhD;
Paul J. Hagerman, MD, PhD;
Davis Hessl, PhD;
Randi J. Hagerman, MD
Arch Neurol. 2008;65(4):495-498.
Background Distal neuropathy is part of the clinical phenotype in most males with the fragile X–associated tremor/ataxia syndrome (FXTAS) caused by the 55 to 200 CGG repeat expansion.
Methods We performed nerve conduction studies in 16 male carriers with FXTAS, 11 non-FXTAS carriers, and 11 control subjects and assessed the outcomes with respect to the fragile X mental retardation 1 genotype (FMR1) (Online Mendelian Inheritance in Man [OMIM] 309550; NT011681) and messenger RNA expression.
Results Men with FXTAS had slower tibial nerve conduction velocities and prolonged F-wave latencies compared with controls (z = 2.06, P = .04; and z = 2.73, P = .005) and unaffected premutation males (z = 1.98, P = .04; and z = 2.00, P = .04). Compound muscle action potential amplitudes were smaller in the FXTAS group relative to controls. Sural nerve action potential amplitudes were reduced in the FXTAS group compared with controls. After controlling for age, there was a significant relationship between the longer CGG repeat number and tibial nerve conduction velocity slowing (r = –0.42, P = .04) and between elevated messenger RNA levels and reduction of the tibial compound muscle action potential velocity (r = –0.52, P = .01) in the permutation group.
Conclusions Male premutation carriers had significant conduction abnormalities of motor and sensory nerves that correlated with molecular measures, suggesting that the premutation FMR1 genotype is a causal factor. There was also evidence of nerve conduction abnormalities in non-FXTAS carriers compared with controls, which suggests that the neuropathy can occur without the full clinical presentation of FXTAS.
Author Affiliations: M.I.N.D. Institute (Drs Soontarapornchai, Fenton-Farrell, P. J. Hagerman, Hessl, and R. J. Hagerman), EMG Laboratory (Dr Maselli), and Departments of Neurology (Dr Maselli), Psychiatry and Behavioral Sciences (Dr Hessl), Biochemistry and Molecular Medicine (Drs Tassone and P. J. Hagerman), and Pediatrics (Dr R. J. Hagerman), University of California, Davis Medical Center, Sacramento.
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