title: NEFL E396K mutation is associated with a novel dominant intermediate Charcot-Marie-Tooth disease phenotype.
abstract: The purpose of the study was to describe a pedigree with NEFL E396K mutation associated with a novel dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) phenotype. The pedigree comprised four patients over two generations, aged between 35 and 59 years, who have been serially evaluated since 1993. Their clinical picture was characterized by pes cavus, sensorimotor neuropathy and spastic gait. Both older patients showed ascending leg weakness to involve pelvic musculature. CMT neuropathy score ranged from 14 to 26 (moderate to severe disease). Electrophysiology showed uniform nerve conduction slowing in the intermediate range, both in distal and proximal nerve segments. Multimodal evoked potential and blink reflex studies revealed abnormalities indicative of central sensorimotor pathway dysfunction. On imaging studies of lower-limb musculature, there was massive atrophy of intrinsic foot muscles and to a lesser degree of calves and thighs predominating in muscles innervated by tibial and sciatic nerves. In both patients exhibiting waddling gait, there was atrophy of pelvic muscles mainly involving gluteus medius, gluteus minimus and piriformis. We conclude that NEFL E396K mutation may manifest with a novel DI-CMT phenotype, characterized by simultaneous involvement of the peripheral and central nervous system.
authors: Service of Neurology, University Hospital "Marqués de Valdecilla (IDIVAL)", University of Cantabria (UC) and "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)", Santander, Spain, jaberciano@humv.es.
authors: José
authors: J
authors: Berciano
authors: Antonio
authors: A
authors: García
authors: Kristien
authors: K
authors: Peeters
authors: Elena
authors: E
authors: Gallardo
authors: Els
authors: E
authors: De Vriendt
authors: Ana L
authors: AL
authors: Pelayo-Negro
authors: Jon
authors: J
authors: Infante
authors: Albena
authors: A
authors: Jordanova
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005071:Evoked Potentials / Q000235:genetics; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L; D005973:Glutamine; D003402:Creatine Kinase; D008239:Lysine