1. Linkage of a new mutation in the proteolipid protein (PLP) gene to Pelizaeus-Merzbacher disease (PMD) in a large Finnish kindred.
- Author
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Pratt VM, Kiefer JR, Lähdetie J, Schleutker J, Hodes ME, and Dlouhy SR
- Subjects
- Base Sequence, DNA Mutational Analysis, DNA, Single-Stranded, Female, Finland, Humans, Male, Molecular Sequence Data, Myelin Proteolipid Protein, Pedigree, Polymorphism, Genetic, X Chromosome, Diffuse Cerebral Sclerosis of Schilder genetics, Genetic Linkage, Myelin Proteins genetics, Point Mutation
- Abstract
The purpose of this study was to confirm linkage of the proteolipid protein gene (PLP) and Pelizaeus-Merzbacher disease (PMD). A T-->A transversion in nucleotide pair 35 of exon 4 of PLP was found in a large Finnish kindred with PMD. This mutation results in the substitution Val165-->Glu165. We used a combination of single-strand conformational polymorphism and PCR primer extension to determine the presence or absence of the point mutation in family members. A lod score of 2.6 (theta = 0) was found for linkage of the gene and the disease. We examined 101 unrelated X chromosomes and found none with the transversion. This is the second report of linkage of PMD to a missense mutation in PLP. These findings support the hypothesis that PMD in this family is a result of the missense mutation present in exon 4 of PLP.
- Published
- 1993