title: SIMPLE mutation analysis in dominant demyelinating Charcot-Marie-Tooth disease: three novel mutations.
abstract: Charcot-Marie-Tooth disease type 1C (CMT1C) is caused by mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE). We analyzed the coding sequence of SIMPLE in DNA of 53 unrelated cases of dominant demyelinating CMT disease with no mutations in PMP22, GJB1, MPZ, EGR2, and NEFL genes. Four different missense mutations were observed in six families. The mutation Gly112Ser was found in two families confirming its frequent occurrence in SIMPLE mutations. Three novel mutations were also identified: Ala111Gly (two families), Pro135Ser, and Pro135Thr. Familial studies revealed that all carriers of mutations (n = 38), aged from 1 to 78 years, were symptomatic, notably children under 10 years (n = 8). Motor conduction velocities in the median nerve ranked from 16.4 to 32.8 m/s (n = 20). In our series of 968 unrelated dominant demyelinating CMT cases (1992-2005), the percentage of SIMPLE mutations was 0.6 (6/968).
authors.affiliation: Neurogénétique, Laboratoire de Biochimie Pédiatrique, Hôpital Debrousse, Lyon, France. philippe.latour@chu-lyon.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Gonnaud
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ollagnon
authors.forename: Victor
authors.initials: V
authors.lastname: Chan
authors.forename: Serge
authors.initials: S
authors.lastname: Perelman
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Claude
authors.initials: C
authors.lastname: Stoll
authors.forename: Christophe
authors.initials: C
authors.lastname: Vial
authors.forename: François
authors.initials: F
authors.lastname: Ziegler
authors.forename: Antoon
authors.initials: A
authors.lastname: Vandenberghe
authors.forename: Irène
authors.initials: I
authors.lastname: Maire
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D020539:Sequence Analysis, Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C118738:LITAF protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors