Abstract
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder that is characterized by dysmyelination of the central nervous system resulting from mutations in the proteolipid protein (PLP) gene. Mutations causing either overexpression or expression of a truncated form of PLP result in oligodendrocyte cell death because of accumulation of PLP in the endoplasmic reticulum. It has therefore been hypothesized that absence of the protein should result in a less severe phenotype. However, until now, only one patient has been described with a complete deletion of the PLP gene. We report a Dutch family with a relatively mild form of PMD, in which the disease cosegregates with a (G-to-A) mutation in the initiation codon of the PLP gene. This mutation should cause the total absence of PLP and is therefore in agreement with the hypothesis that absence of PLP leads to a mild form of PMD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Eiken HG, Knappskog PM, Apold J, Skjelkvale L, Boman H (1992) A de novo phenylketonuria mutation: ATG (Met) to ATA (Ile) in the start codon of the phenylalanine hydroxylase gene. Hum Mutat 1:388–391
Gow A, Friedrich VL Jr, Lazzarini RA (1994) Many natural occurring mutations of myelin proteolipid protein impair its intracellular transport. J Neurosci Res 37:574–583
Kagawa T, Ikenaka K, Inoue Y, Kuriyama S, Tsujii T, Nakao J, Nakajima K, Aruga J, Okano H, Mikoshiba K (1994) Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein gene. Neuron 13:427–442
Mukhopadhyay A, Uh M, Mueller DM (1994) Level of ATP synthase activity required for yeast Saccharomyces cerevisiae to grow on glycerol media. FEBS Lett 343:160–164
Raskind WH, Williams CA, Hudson LD, Bird TD (1991) Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease. Am J Hum Genet 49:1355–1360
Saba L, Meloni A, Sardu R, Travi M, Primignani P, Rosatelli MC, Cao A (1992) A novel beta-thalassemia mutation (G->A) at the initiation codon of the beta-globin gene. Hum Mut 1:420–422S
Strautnieks S, Rutland P, Winter R, Barcutser M, Malcolm S (1992) Pelizaeus-Merzbacher disease: Detection of mutations Thr181arPro and Leu223→Wro in the proteolipid protein, and prenatal diagnosis Am J Hum Genet 51:871–878
Usui M, Sembongi H, Matsuzaki H, Matsumoto K, Shibuya I (1994) Primary structures of the wild-type and mutant alleles encoding the phophatidylglycerophosphate synthase of Escherichia coli. J Bacteriol 176:3389–3392
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sistermans, E.A., de Wijs, S., de Coo, R.F.M. et al. A (G-to-A) mutation in the initiation codon of the proteolipid protein gene causing a relatively mild form of Pelizaeus-Merzbacher disease in a Dutch family. Hum Genet 97, 337–339 (1996). https://doi.org/10.1007/BF02185767
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02185767