title: Reduced penetrance in hereditary motor neuropathy caused by TRPV4 Arg269Cys mutation.
abstract: Incomplete penetrance has rarely been reported in Charcot-Marie-Tooth disease. Our aim is to describe reduced penetrance in a hereditary motor neuropathy pedigree due to mutation in the transient receptor potential vallinoid 4 (TRPV4) gene. The pedigree comprised two affected members, the proband aged 44 years and her affected daughter aged 7 years, and seven additional related subjects, three of whom were subclinical gene mutation carriers aged 9, 40 and 70 years. Clinico-electrophysiological studies, MRI of lower-limb musculature and genetic testing of the TRPV4 were performed. The proband presented with a moderate facio-scapulo-peroneal syndrome, whereas her symptomatic daughter suffered from severe congenital spinal muscular atrophy with arthrogryposis, laryngomalacia, and vocal cord paresis. Electrophysiological evaluation revealed a pure motor axonal neuropathy. In the proband, MRI showed extensive and widespread fatty atrophy of lower-leg musculature, whereas in thigh musculature there was just mild distal fatty infiltration of vastus lateralis. Genetic testing revealed a heterozygous Arg269Cys mutation in the TPRV4 gene. In all three mutation carriers results from clinical and electrophysiological examination, and MRI of foot and lower-leg musculature were normal. We conclude that non-penetrance may be an integral feature of neuropathic syndromes associated with TRPV4 gene mutation.
authors.affiliation: Service of Neurology, University Hospital "Marqués de Valdecilla" (IFIMAV), "Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas" (CIBERNED), University of Cantabria (UC), 39008 Santander, Spain. jaberciano@humv.es
authors.forename: José
authors.initials: J
authors.lastname: Berciano
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baets
authors.forename: Elena
authors.initials: E
authors.lastname: Gallardo
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zimoń
authors.forename: Antonio
authors.initials: A
authors.lastname: García
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Laso
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D004576:Electromyography; D005260:Female; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human