title: The Roussy-Lévy family: from the original description to the gene.
abstract: In 1926, Roussy and Lévy described a large family whose members manifested an early onset dominantly inherited gait ataxia, pes cavus, and areflexia, which was eventually associated with distal muscle atrophy, postural tremor, and minor sensory loss. Slow nerve conduction and demyelination of nerve fibers with onion bulb formations in nerve biopsy specimens led to the Roussy-Lévy syndrome (RLS) being considered a variant of demyelinating Charcot-Marie-Tooth disease (CMT-1). In the present article, we report on the long-term follow-up, on nerve biopsy findings, and on the underlying molecular genetic defect in members of the original family studied by Roussy and Lévy. All patients were able to walk during their seventh decade of life. Morphologically, a chronic demyelinating neuropathy with the remarkable aspects of a focally hypertrophic myelin sheath and major loss of myelinated fibers was observed in nerve biopsy specimens of 3 members of this family. Molecular genetic testing identified a previously unknown heterozygous missense point mutation which yielded an Asn131Lys substitution in the extracellular domain of the myelin protein zero (P0). These findings show that the Roussy-Lévy family belongs to the CMT-1B subtype and has original morphological and genetic features.
authors.affiliation: Department of Neurology, Centre Hospitalier-Universitaire de Bicêtre, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: V
authors.initials: V
authors.lastname: Planté-Bordeneuve
authors.forename: A
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: C
authors.initials: C
authors.lastname: Lacroix
authors.forename: J
authors.initials: J
authors.lastname: Lapresle
authors.forename: G
authors.initials: G
authors.lastname: Said
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018993:Myelin P0 Protein / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010375:Pedigree; D013497:Sural Nerve / Q000473:pathology; D013997:Time Factors
chemical_list: D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human