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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Jul;51(1):161–169.

Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus-Merzbacher disease.

R Doll 1, M R Natowicz 1, R Schiffmann 1, F I Smith 1
PMCID: PMC1682866  PMID: 1376966

Abstract

Pelizaeus-Merzbacher disease (PMD) is a clinically heterogeneous, slowly progressive leukodystrophy. The recent detection of mutations in the myelin proteolipid protein (PLP) gene in several PMD patients offers the opportunity both to design DNA-based tests that would be useful in diagnosing a proportion of PMD cases and, in particular, to evaluate the diagnostic utility of single-strand conformation polymorphism (SSCP) analysis for this disease. A combination of SSCP analysis and direct sequencing of PCR-amplified DNA was used to screen for PLP mutations in 24 patients affected with leukodystrophies of unknown etiology. Two heretofore undescribed mutations in the PLP gene were identified, Asp202His in exon 4 and Gly73Arg in exon 3. The ease and efficiency of SSCP analysis in detecting new mutations support the utilization of this technique in screening for PLP mutations in patients with unexplained leukodystrophies.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boulloche J., Aicardi J. Pelizaeus-Merzbacher disease: clinical and nosological study. J Child Neurol. 1986 Jul;1(3):233–239. doi: 10.1177/088307388600100310. [DOI] [PubMed] [Google Scholar]
  2. Diehl H. J., Schaich M., Budzinski R. M., Stoffel W. Individual exons encode the integral membrane domains of human myelin proteolipid protein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9807–9811. doi: 10.1073/pnas.83.24.9807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gencic S., Abuelo D., Ambler M., Hudson L. D. Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein. Am J Hum Genet. 1989 Sep;45(3):435–442. [PMC free article] [PubMed] [Google Scholar]
  4. Gencic S., Hudson L. D. Conservative amino acid substitution in the myelin proteolipid protein of jimpymsd mice. J Neurosci. 1990 Jan;10(1):117–124. doi: 10.1523/JNEUROSCI.10-01-00117.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hayashi K. PCR-SSCP: a simple and sensitive method for detection of mutations in the genomic DNA. PCR Methods Appl. 1991 Aug;1(1):34–38. doi: 10.1101/gr.1.1.34. [DOI] [PubMed] [Google Scholar]
  6. Hudson L. D., Friedrich V. L., Jr, Behar T., Dubois-Dalcq M., Lazzarini R. A. The initial events in myelin synthesis: orientation of proteolipid protein in the plasma membrane of cultured oligodendrocytes. J Cell Biol. 1989 Aug;109(2):717–727. doi: 10.1083/jcb.109.2.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hudson L. D., Puckett C., Berndt J., Chan J., Gencic S. Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8128–8131. doi: 10.1073/pnas.86.20.8128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Laursen R. A., Samiullah M., Lees M. B. The structure of bovine brain myelin proteolipid and its organization in myelin. Proc Natl Acad Sci U S A. 1984 May;81(9):2912–2916. doi: 10.1073/pnas.81.9.2912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nadon N. L., Duncan I. D., Hudson L. D. A point mutation in the proteolipid protein gene of the 'shaking pup' interrupts oligodendrocyte development. Development. 1990 Oct;110(2):529–537. doi: 10.1242/dev.110.2.529. [DOI] [PubMed] [Google Scholar]
  10. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  11. Pham-Dinh D., Popot J. L., Boespflug-Tanguy O., Landrieu P., Deleuze J. F., Boué J., Jollès P., Dautigny A. Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7562–7566. doi: 10.1073/pnas.88.17.7562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Popot J. L., Pham Dinh D., Dautigny A. Major Myelin proteolipid: the 4-alpha-helix topology. J Membr Biol. 1991 Mar;120(3):233–246. doi: 10.1007/BF01868534. [DOI] [PubMed] [Google Scholar]
  13. Pratt V. M., Trofatter J. A., Schinzel A., Dlouhy S. R., Conneally P. M., Hodes M. E. A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease. Am J Med Genet. 1991 Jan;38(1):136–139. doi: 10.1002/ajmg.1320380129. [DOI] [PubMed] [Google Scholar]
  14. Shaw S. Y., Laursen R. A., Lees M. B. Identification of thiol groups and a disulfide crosslink site in bovine myelin proteolipid protein. FEBS Lett. 1989 Jul 3;250(2):306–310. doi: 10.1016/0014-5793(89)80744-6. [DOI] [PubMed] [Google Scholar]
  15. Stoffel W., Hillen H., Giersiefen H. Structure and molecular arrangement of proteolipid protein of central nervous system myelin. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5012–5016. doi: 10.1073/pnas.81.16.5012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Theophilus B., Latham T., Grabowski G. A., Smith F. I. Gaucher disease: molecular heterogeneity and phenotype-genotype correlations. Am J Hum Genet. 1989 Aug;45(2):212–225. [PMC free article] [PubMed] [Google Scholar]
  17. Trofatter J. A., Dlouhy S. R., DeMyer W., Conneally P. M., Hodes M. E. Pelizaeus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9427–9430. doi: 10.1073/pnas.86.23.9427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Trofatter J. A., Pratt V. M., Dlouhy S. R., Hodes M. E. AhaII polymorphism in human X-linked proteolipid protein gene (PLP). Nucleic Acids Res. 1991 Nov 11;19(21):6057–6057. doi: 10.1093/nar/19.21.6057-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weimbs T., Dick T., Stoffel W., Boltshauser E. A point mutation at the X-chromosomal proteolipid protein locus in Pelizaeus-Merzbacher disease leads to disruption of myelinogenesis. Biol Chem Hoppe Seyler. 1990 Dec;371(12):1175–1183. doi: 10.1515/bchm3.1990.371.2.1175. [DOI] [PubMed] [Google Scholar]

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