Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Oct;51(4):871–878.

Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis.

S Strautnieks 1, P Rutland 1, R M Winter 1, M Baraitser 1, S Malcolm 1
PMCID: PMC1682779  PMID: 1384324

Abstract

A family with an apparent history of X-linked Pelizaeus-Merzbacher disease presented for genetic counseling, requesting carrier detection and prenatal diagnosis. RFLP analysis using the proteolipid protein (PLP) gene probe was uninformative in this family. A prenatal diagnosis on a chorionic villus sample (CVS) was carried out using single-strand conformation polymorphism (SSCP) analysis of a variant in exon 4 of the PLP gene. The fetus was predicted to be unaffected. Sequencing of the exon from the CVS, the predicted-carrier mother, and the obligate-carrier grandmother revealed an A-to-C change at nucleotide 541 in the two women but not in the fetus. As this change results in a Thr-to-Pro change at amino acid 181 in a region of the gene predicted to be part of a transmembrane segment, it was concluded that this was the mutation causing the disease in this family. In addition, in a second family, an exon 5 variant band pattern on SSCP analysis was shown by sequencing to be due to a T-to-C change at nucleotide 668. This results in a Leu-to-Pro change in a carrier mother and in her two affected sons. These results provide further examples of mutations in PLP that cause Pelizaeus-Merzbacher disease and illustrate the value of SSCP in genetic analysis.

Full text

PDF
875

Images in this article

875Figure 2
on p.875
875Figure 3
on p.875
876Figure 4
on p.876
876Figure 5
on p.876
877Figure 6
on p.877

Selected References

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

  1. Begleiter M. L., Harris D. J. Autosomal recessive form of connatal Pelizaeus-Merzbacher disease. Am J Med Genet. 1989 Jul;33(3):311–313. doi: 10.1002/ajmg.1320330305. [DOI] [PubMed] [Google Scholar]
  2. Boltshauser E., Schinzel A., Wichmann W., Haller D., Valavanis A. Pelizaeus-Merzbacher disease: identification of heterozygotes with magnetic resonance imaging? Hum Genet. 1988 Dec;80(4):393–394. doi: 10.1007/BF00273659. [DOI] [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. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [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., 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]
  7. Jeanpierre M. A rapid method for the purification of DNA from blood. Nucleic Acids Res. 1987 Nov 25;15(22):9611–9611. doi: 10.1093/nar/15.22.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Pelletier J., Bruening W., Kashtan C. E., Mauer S. M., Manivel J. C., Striegel J. E., Houghton D. C., Junien C., Habib R., Fouser L. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991 Oct 18;67(2):437–447. doi: 10.1016/0092-8674(91)90194-4. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Scheffer I. E., Baraitser M., Wilson J., Harding B., Kendall B., Brett E. M. Pelizaeus-Merzbacher disease: classical or connatal? Neuropediatrics. 1991 May;22(2):71–78. doi: 10.1055/s-2008-1071420. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Tassabehji M., Read A. P., Newton V. E., Harris R., Balling R., Gruss P., Strachan T. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature. 1992 Feb 13;355(6361):635–636. doi: 10.1038/355635a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Wu J. S., Riordan J. R., Willard H. F., Milner R., Kidd K. K. MSP RFLP for X-linked proteolipid protein gene (PLP) identified with either rat or human PLP cDNA clone. Nucleic Acids Res. 1987 Feb 25;15(4):1882–1882. doi: 10.1093/nar/15.4.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES