Abnormal nerve conduction features in fragile X premutation carriers.
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.
Soontarapornchai
Kultida
K
M.I.N.D. Institute, University of California-Davis Medical Center, Sacramento, CA 95817, USA.
Maselli
Ricardo
R
Fenton-Farrell
Grace
G
Tassone
Flora
F
Hagerman
Paul J
PJ
Hessl
Davis
D
Hagerman
Randi J
RJ
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000368:Aged; D004252:DNA Mutational Analysis; D004576:Electromyography; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009132:Muscles / Q000294:innervation; D009431:Neural Conduction / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D011984:Sensory Receptor Cells / Q000503:physiopathology; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D013497:Sural Nerve / Q000503:physiopathology; D013979:Tibial Nerve / Q000503:physiopathology; D014202:Tremor / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D018911:Trinucleotide Repeats
D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human