title: Déjerine-Sottas syndrome with a silent nucleotide change of myelin protein zero gene.
abstract: Charcot-Marie-Tooth disease type 1B (CMT1B) and Déjerine-Sottas syndrome type B (DSSB) are caused by missense or frameshift mutations of myelin protein zero (MPZ) gene. We identified an apparently silent synonymous c.411C>T transition in MPZ exon 3 (p.Gly137Gly) which segregated with DSS in a two-generation pedigree. Retro-transcriptional analysis of MPZ in the proband's archive sural nerve biopsy identified an r.410_448del mutant transcript which resulted from an activated cryptic splice site in exon 3 and led to an in-frame partial deletion of exon 3 (p.Gly137_Lys149del). Quantitative real-time polymerase chain reaction (QRT-PCR) compared with two unrelated CMT1B nerves carrying a frameshift c.306delA mutation (p.Asp104ThrfsX13) indicated that the r.410_448del was stable differing from the p.Asp104ThrfsX13-associated transcript which was subjected to nonsense-mediated decay. The report highlighted the possible pathogenic role of synonymous MPZ mutations and difficulties in interpreting results from routine mutational screenings.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Taioli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cabrini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cavallaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Silvia
authors.initials: S
authors.lastname: Testi
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
mesh_terms: D005260:Female; D016368:Frameshift Mutation; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018993:Myelin P0 Protein / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D055815:Young Adult
chemical_list: D018993:Myelin P0 Protein