A de novo splice donor site mutation causes in-frame deletion of 14 amino acids in the proteolipid protein in Pelizaeus-Merzbacher disease.
Pelizaeus-Merzbacher disease (PMD) is a leukodystrophy associated with mutations in the proteolipid protein (PLP) gene. Jimpy is a mouse model of human PMD, and a splice site mutation in Jimpy causes the deletion of exon 5 from the PLP mRNA, producing a truncated form of PLP. We describe a de novo point mutation at the 5' splice donor site of exon 5 in a 17-year-old male with PMD, which results in the skipping of 42 base pairs of exon 5. The mutation removes only 14 amino acids in-frame of PLP. This is a novel splice donor site mutation in the human PLP gene. Moreover, the results indicate that the 14-amino acid deletion in the PLP is responsible for oligodendrocyte cell death and the development of PMD.
Aoyagi
Y
Y
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Kobayashi
H
H
Tanaka
K
K
Ozawa
T
T
Nitta
H
H
Tsuji
S
S
D000293:Adolescent; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D017384:Sequence Deletion