title: Congenital hypomyelinating neuropathy due to a novel MPZ mutation.
abstract: Congenital hypomyelinating neuropathy (CHN) is a severe inherited neuropathy with neonatal or early infancy onset, reduced nerve conduction velocity, and pathological evidence of hypomyelination. We describe a case of CHN that presented with neonatal hypotonia and a progressive downhill clinical course, developing cranial nerve dysfunction, and respiratory failure. The nerve conduction velocities were severely slowed and sural nerve biopsy revealed non-myelinated and poorly myelinated axons, with no typical onion bulbs. The mutational screening showed that our proband harbored a novel missense mutation, p.S121F, in the MPZ gene. In silico analyses and molecular modeling predicted that the replacement of a serine by a phenylalanine is a non-tolerated change and may affect the folding and the stability of the protein. Subcellular location studies were performed and revealed that the mutant protein loses its correct location on the cell membrane surface and is mainly expressed in the cytosol, reducing its adhesive properties. This case illustrates the clinical heterogeneity that exists in neuropathies associated with MPZ mutations and highlights that in patients with mild hypotonia in the first months that develop a very severe demyelinating neuropathy, the MPZ gene must be taken into account.
authors.affiliation: Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. sevilla_ter@gva.es
authors.forename: Teresa
authors.initials: T
authors.lastname: Sevilla
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lupo
authors.forename: Rafael
authors.initials: R
authors.lastname: Sivera
authors.forename: Clara
authors.initials: C
authors.lastname: Marco-Marín
authors.forename: Dolores
authors.initials: D
authors.lastname: Martínez-Rubio
authors.forename: Eloy
authors.initials: E
authors.lastname: Rivas
authors.forename: Arturo
authors.initials: A
authors.lastname: Hernández
authors.forename: Francesc
authors.initials: F
authors.lastname: Palau
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinós
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D018993:Myelin P0 Protein / Q000235:genetics*
chemical_list: C560547:MPZ protein, human; D018993:Myelin P0 Protein