title: Protein truncation test: analysis of two novel point mutations at the carboxy-terminus of the human dystrophin gene associated with mental retardation.
abstract: Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-terminating mutations. A number of data raised the possibility that the C-terminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutations in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation termination of dystrophin. The possible effects on the reading frame were analyzed by the study of reverse transcripts amplified from peripheral blood lymphocytes mRNA and by the protein truncation test.
authors.affiliation: Laboratoire de Biochimie Génétique, INSERM U249/CNRS UPR 9008, Institut de Biologie, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Tuffery
authors.forename: U
authors.initials: U
authors.lastname: Lenk
authors.forename: R G
authors.initials: RG
authors.lastname: Roberts
authors.forename: C
authors.initials: C
authors.lastname: Coubes
authors.forename: J
authors.initials: J
authors.lastname: Demaille
authors.forename: M
authors.initials: M
authors.lastname: Claustres
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D010443:Peptide Chain Termination, Translational; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D016189:Dystrophin