Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene

Abstract

A MUTATION at codon 717 of the β-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family1. This mutation has been reported in a further five out of 100 families multiply affected by Alzheimer's disease1–4. We have identified another family, F19, in which we have detected linkage between the β-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 (ref. 5) in affected individuals from this family has revealed a base change producing a Val → Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Goate, A. et al. Nature 349, 704–706 (1991).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Hardy, J. et al. Lancet 337, 1342–1343 (1991).

    Google Scholar 

  3. 3

    van Duijn, C. M. et al. Lancet 337, 978 (1991).

    CAS  Article  Google Scholar 

  4. 4

    Naruse, S. et al. Lancet 337, 978–979 (1991).

    CAS  Article  Google Scholar 

  5. 5

    Yoshikai, S., Sasaki, H., Dohura, K., Furuya, H. & Sakaki, Y. Gene 87, 257–263 (1990).

    CAS  Article  Google Scholar 

  6. 6

    Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Genomics 5, 874–879 (1989).

    CAS  Article  Google Scholar 

  7. 7

    Orita, M., Sekiya, T. & Hayashi, K. Genomics 8, 271–278 (1990).

    CAS  Article  Google Scholar 

  8. 8

    McKhann, G. et al. Neurology 34, 939–944 (1984).

    CAS  Article  Google Scholar 

  9. 9

    Tanzi, R. E. & Hyman, B. T. Nature 350, 564 (1991).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Rumble, B. et al. New Engl. J. Med. 320, 1446–1452 (1989).

    CAS  Article  Google Scholar 

  11. 11

    Johnstone, E. M., Chaney, M. O., Norris, F. H., Pascual, R. & Little, S. P. Molec. Brain Res. 10, 299–305 (1991).

    CAS  Article  Google Scholar 

  12. 12

    Klausner, R. D. & Harford, J. B. Science 246, 870–872 (1989).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Harrison, P. J., Barton, A. J. L. & Pearson, R. C. A. Neuro Rep. 2, 152–154 (1991).

    CAS  Google Scholar 

  14. 14

    Esch, F. S. et al. Science 248, 1122–1124 (1990).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Master, C. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4245–4249 (1985).

    ADS  Article  Google Scholar 

  16. 16

    Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 120, 885–890 (1984).

    CAS  Article  Google Scholar 

  17. 17

    Lathrop, G., Lalouel, J. M., Julier, C. & Ott, J. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 1984).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Charter Harlin, M. C. et al. Neurosci. Lett. 129, 134–135 (1991).

    Article  Google Scholar 

  19. 19

    Levy, E. et al. Science 248, 1124–1126 (1990).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Murrell, J., Farlow, M., Ghetti, B. & Benson, M. Science 253, 97–98 (1991).

    ADS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chartier-Harlin, M., Crawford, F., Houlden, H. et al. Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353, 844–846 (1991). https://doi.org/10.1038/353844a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing