title: Complexity of the Hereditary Motor and Sensory Neuropathies: Clinical and Cellular Characterization of the MPZ p.D90E Mutation.
abstract: Early-onset hereditary motor and sensory neuropathies are rare diseases representing a broad clinical and genetic spectrum. Without a notable familial history, the clinical diagnosis is complicated because acquired causes of peripheral neuropathy, such as inflammatory neuropathies, neuropathies with toxic causes, and nutritional deficiencies, must be considered. We examined the clinical, electrophysiological, and pathologic manifestations of a boy with an initial diagnosis of chronic inflammatory demyelinating polyneuropathy. The progression of the disease despite treatment led to a suspicion of hereditary motor and sensory neuropathy. Genetic testing revealed the presence of the MPZ p.D90E mutation in heterozygosis. To clarify the pathogenicity of this mutation and achieve a conclusive diagnosis, we investigated the MPZ p.D90E mutation through in silico and cellular approaches. This study broadens the clinical phenotype of hereditary motor and sensory neuropathy due to MPZ mutation and emphasises the difficulty of achieving an accurate genetic diagnosis in a sporadic patient to provide an appropriate pharmacologic treatment.
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lupo
authors.affiliation: Neuropediatrics Department, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Pascual-Pascual
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Sancho
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calpena
authors.affiliation: Neuropathology Department, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gutiérrez-Molina
authors.affiliation: Neuropediatrics Department, Hospital Universitario de Guadalajara, Guadalajara, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Mateo-Martínez
authors.affiliation: Centro de Investigación Príncipe Felipe (CIPF), CIPF associated unit to the IBV-CSIC, Valencia, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, CIBERER, Valencia, Spain Genetics Department, University of Valencia, Valencia, Spain cespinos@cipf.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinós
authors.affiliation: Neuropediatrics Department, Hospital Universitario de Guadalajara, Guadalajara, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Arriola-Pereda
mesh_terms: D002675:Child, Preschool; D018450:Disease Progression; D006367:HeLa Cells; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology
chemical_list: C560547:MPZ protein, human; D018993:Myelin P0 Protein
keywords: MPZ gene; aggregation assay; de novo mutation; hereditary motor and sensory neuropathy; inflammatory neuropathy