title: A novel NDRG1 mutation in a non-Romani patient with CMT4D/HMSN-Lom.
abstract: Charcot-Marie-Tooth disease type 4D (CMT4D), also known as hereditary motor and sensory neuropathy Lom type (HMSNL), is an autosomal recessive, early onset, severe demyelinating neuropathy with hearing loss, caused by N-Myc downstream-regulated gene 1 (NDRG1) mutations. CMT4D is rare with only three known mutations, one of which (p.Arg148Ter) is found in patients of Romani ancestry and accounts for the vast majority of cases. We report a 38-year-old Italian female with motor development delay, progressive neuropathy, and sensorineural deafness. Magnetic resonance imaging showed slight atrophy of cerebellum, medulla oblongata, and upper cervical spinal cord. She had a novel homozygous NDRG1 frameshift mutation (c.739delC; p.His247ThrfsTer74). The identification of this NDRG1 mutation confirms that CMT4D is not a private Romani disease and should be considered in the differential diagnosis of recessive demyelinating CMT.
authors.affiliation: Unit of Rare Neurological Diseases of Adulthood, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Piscosquito
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Department of Diagnostics and Applied Technology, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Magri
authors.affiliation: Unit of Rare Neurological Diseases of Adulthood, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Saveri
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Department of Diagnostics and Applied Technology, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Milani
authors.affiliation: Neurophysiopathology and Epilepsy Centre, Department of Diagnostics and Applied Technology, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciano
authors.affiliation: Unit of Neuroradiology, Department of Diagnostics and Applied Technology, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Farina
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Department of Diagnostics and Applied Technology, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.affiliation: Unit of Rare Neurological Diseases of Adulthood, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D002531:Cerebellum / Q000000981:diagnostic imaging; D002607:Charcot-Marie-Tooth Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008526:Medulla Oblongata / Q000000981:diagnostic imaging; D009154:Mutation / Q000235:genetics*; D012035:Refsum Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D013116:Spinal Cord / Q000000981:diagnostic imaging; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: CMT4; Charcot-Marie-Tooth disease; N-Myc downstream-regulated gene 1 (NDRG1); demyelinating recessive CMT; hereditary motor and sensory neuropathy Lom type