A novel point mutation in the peripheral myelin protein 22 (PMP22) gene associated with Charcot-Marie-Tooth disease type 1A
| Autor: | Maria Giovanna Marrosu, C. Cianchetti, Francesco Muntoni, A. Vannelli, S. Vaccargiu, Giovanni Marrosu |
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| Rok vydání: | 1997 |
| Předmět: |
Genetics
Base Sequence Genetic Linkage Point mutation Molecular Sequence Data Nonsense mutation Sequence Analysis DNA Biology Charcot-Marie-Tooth Disease Type 1A Polymerase Chain Reaction Pedigree Chromosome 17 (human) Transmembrane domain Exon Charcot-Marie-Tooth Disease Peripheral myelin protein 22 Humans Point Mutation Missense mutation Neurology (clinical) Myelin Proteins |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.48.2.489 |
| Popis: | Article abstract-We studied the peripheral myelin protein gene PMP-22 in a large Sardinian family with Charcot-Marie-Tooth disease type 1A (CMT1A), in which the duplication commonly found in CMT1A was absent, but with evidence of linkage on chromosome 17. Sequencing of DNA and cDNA showed a missense point mutation G 368 [arrow right] T in exon 5 of PMP22, predicted to determine a valine for glycine substitution at codon 107, which could be ploted in the center of the PMP22 protein putative transmembrane domain III. Using sequence-specific oligonucleotide probes (SSOP), we found the point mutation in all affected CMT1A subjects but not in healthy family members or in 314 chromosomes of controls, thus indicating that the G 368 [arrow right] T point mutation is not a polymorphism. In the hypothetical model of PMP22, the amino acid at position 107 plots deeply into alpha-helical transmembrane domain III, a domain where point mutations have never previously been found. Although the same mutation was present in all CMT1A subjects examined, clinical findings showed a different stereotyped pattern in relation to the generation examined, for a progressive increase in severity and an earlier onset from the first to the third generation examined. Molecular analysis suggests that CMT1A disease in this family is due to the G 368 [arrow right] T point mutation, although other mechanisms may account for the clinical variability in the members of different generations. NEUROLOGY 1997;48: 489-493 |
| Databáze: | OpenAIRE |
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