title: A novel stop codon mutation in the PMP22 gene associated with a variable phenotype.
abstract: The most frequent inherited peripheral neuropathy is the peripheral myelin protein 22 (PMP22) gene related disease. Duplication, deletion, and point mutations in that gene are associated with phenotypic variability. Here we report a family carrying a novel mutation in the PMP22 gene (c. 327C>A), which results in a premature stop codon (Cys109stop). The family members who carry this mutation have a Charcot-Marie-Tooth type 1 variable phenotype, ranging from asymptomatic to severely affected. These findings suggest that the fourth transmembrane domain of the PMP22 gene may play an important role, although the intrafamilial clinical variability reinforces the observation that pathogenic mutations are not always phenotype determinant and that other factors (genetic or epigenetic) modulate the severity of the clinical course.
authors.affiliation: Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matao 277 CEP, São Paulo 05508-900, Brazil.
authors.forename: K T
authors.initials: KT
authors.lastname: Abe
authors.forename: A M M
authors.initials: AM
authors.lastname: Lino
authors.forename: M T A
authors.initials: MT
authors.lastname: Hirata
authors.forename: R C M
authors.initials: RC
authors.lastname: Pavanello
authors.forename: M W I
authors.initials: MW
authors.lastname: Brotto
authors.forename: P E
authors.initials: PE
authors.lastname: Marchiori
authors.forename: M
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D001706:Biopsy / Q000379:methods; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D018388:Codon, Terminator / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D009460:Neurologic Examination / Q000379:methods; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013497:Sural Nerve / Q000473:pathology / Q000648:ultrastructure
chemical_list: D018388:Codon, Terminator; D009185:Myelin Proteins; C073687:PMP22 protein, human; D003545:Cysteine