Linkage of a new mutation in the proteolipid protein (PLP) gene to Pelizaeus-Merzbacher disease (PMD) in a large Finnish kindred.
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.
Pratt
V M
VM
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251.
Kiefer
J R
JR
Lähdetie
J
J
Schleutker
J
J
Hodes
M E
ME
Dlouhy
S R
SR
D001483:Base Sequence; D004252:DNA Mutational Analysis; D004277:DNA, Single-Stranded; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005260:Female; D005387:Finland; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014960:X Chromosome
D004277:DNA, Single-Stranded; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein