Rare myelin protein zero sequence variant in late onset CMT1B

• Published in: Journal of the neurological sciences Vol. 263; no. 1; pp. 177 - 179
• Main Authors: Souayah, Nizar, Seltzer, W.K, Brannagan, Thomas H, Chin, Russell L, Sander, Howard W
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.12.2007; Elsevier Science
• Subjects: Aged; Axonal; Biological and medical sciences; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - physiopathology; Charcot–Marie–Tooth; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Errors of metabolism; Family Health; Female; Hereditary; Histidine - genetics; Humans; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous hereditary metabolic disorders; Mutation; Mutation - genetics; Myelin P0 Protein - genetics; Myelin protein 0; Neural Conduction - physiology; Neurology; Neuropathy; Proline - genetics; CMAP; sensory nerve action potential; Charcot–Marie–Tooth; CMT; Neuropathy; SNAP; Hereditary; myelin protein 0; compound muscle action potential; m/s; CV; MPZ; meter per second; conduction velocity; Mutation; Axonal; Myelin protein 0; Neuromuscular diseases; Nervous system diseases; Myelin; Charcot-Marie-Tooth; Protein; Genetic disease; Charcot-Marie-Tooth disease; Central nervous system disease; Degenerative disease; Spinal cord disease; Aminoacid sequence
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2007.05.020

Abstract Myelin protein zero (MPZ) mutations cause demyelinating neuropathies that range from severe neonatal to milder adult forms. We report a 65-year-old woman with slowly progressive leg weakness starting at 47. Examination revealed distal weakness and atrophy in all extremities, impaired light touch in both feet and pin perception to proximal calves, absent leg reflexes, and unsteady gait. Electrodiagnostic studies revealed a severe sensorimotor polyneuropathy with conduction velocities of 25  m/s – to normal. The conduction velocities in the upper 20's were seen in lower extremities with severe reduction of the corresponding compound muscle action potential amplitudes. She had a MPZ mutation with A–C transversion (nucleotide: 116, codon: 10, histidine-to-proline). Her sister has an identical mutation, with high arches, distal leg weakness, decreased vibration sensation in toes and ankle areflexia. Nerve conduction studies revealed a moderate–severe sensorimotor polyneuropathy with nerve conduction velocities of 36  m/s – to normal. Their mother had an abnormal gait and conduction velocities of 29–30  m/s. A third sister is clinically and genetically unaffected. One report has previously described four patients with this mutation with similar clinical and electrodiagnostic features. In patients tested for possible CMT, the frequency of MPZ His–Pro codon 10 substitutions was 0.11% (27 of 24,076 alleles).