title: Abnormal nerve conduction features in fragile X premutation carriers.
abstract: 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.
authors.affiliation: M.I.N.D. Institute, University of California-Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Kultida
authors.initials: K
authors.lastname: Soontarapornchai
authors.forename: Ricardo
authors.initials: R
authors.lastname: Maselli
authors.forename: Grace
authors.initials: G
authors.lastname: Fenton-Farrell
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Davis
authors.initials: D
authors.lastname: Hessl
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: 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
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human