Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Dejerine–Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene


Dejerine–Sottas syndrome is a hypertrophic, demyelinating neuropathy which appears to demonstrate autosomal recessive inheritance in most pedigrees. Clinical symptoms are similar but more severe than Charcot–Marie–Tooth disease type 1 (CMT1), of which the major subtype, CMT1 A, results either from duplication of a 1.5–megabase DNA region in chromosome 17p11.2–p12 containing the myelin gene PMP22, or from PMP22 point mutation. Mutational analysis of the PMP22 coding region in two unrelated Dejerine–Sottas patients identified individual missense point mutations present in the heterozygous state. These findings suggest that Dejerine–Sottas syndrome can result from dominant point mutation alleles of PMP22.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Dejerine, J. & Sottas, J. Sur la nevrite interstitielle, hypertrophique et progressive de l'enfance. Comptes Rendus de la Societe de Biologie Paris 45, 63–96 (1893).

    Google Scholar 

  2. 2

    Dyck, P.J., Chance, P., Lebo, R. & Carney, A.J. . in Peripheral Neuropathy (eds Dyck, P.J. et al.) 1094–1136 (Saunders, Philadelphia, 1993).

    Google Scholar 

  3. 3

    Dyck, P.J. & Gomez, M.R. Segmental demyelinization in Dejerine-Sottas disease: light, phase-contrast, and electron microscopic studies. Mayo Clin. Proc. 43, 280–296 (1968).

    CAS  PubMed  Google Scholar 

  4. 4

    Dyck, P.J., Lambert, E.H., Sanders, K. & O'Brien, P.C. Severe hypomyelination and marked abnormality of conduction in Dejerine-Sottas hypertrophic neuropathy: myelin thickness and compound action potential of sural nerve in vitro. Mayo Clin. Proc. 46, 432–436 (1971).

    CAS  PubMed  Google Scholar 

  5. 5

    Dyck, P.J. & Lambert, E.H. Lower motor and primary sensory neuron disease with peroneal muscular atrophy I. Neurologic, genetic and electrophysiological findings in hereditary polyneuropathies. Arch. Neurol. 18, 603–618 (1968).

    CAS  Article  Google Scholar 

  6. 6

    Charcot, J.-M. & Marie, P. Sur une forme particuliere d'atrophie musculaire progressive, souvent familiale, debutant par les pieds et les jambes et atteignant plus tard les mains. Rev. Med. 6, 97–138 (1886).

    Google Scholar 

  7. 7

    Tooth, H.H., The Peroneal Type of Progressive Muscular Atrophy (H.K. Lewis, London, 1886).

    Google Scholar 

  8. 8

    Lupski, J.R., Garcia, C.A., Parry, G.J. & Patel, P.I. . in Current Neurology (ed. Appel, S.) 1–25 (Mosby-Yearbook, Chicago, 1991).

    Google Scholar 

  9. 9

    Beighton, P. & Beighton, G. in The Man Behind the Syndrome 26–27 (Springer, Berlin, 1886).

    Google Scholar 

  10. 10

    McCusick, V.A. Mendelian Inheritance in Man (10th edn) (Johns Hopkins University Press, Baltimore, 1992).

    Google Scholar 

  11. 11

    Lupski, J.R. et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell 66, 219–232 (1991).

    CAS  Article  Google Scholar 

  12. 12

    Raeymaekers, P. et al. Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). Neuromusc. Disorders 1, 93–97 (1991).

    CAS  Article  Google Scholar 

  13. 13

    Wise, C.A. et al. Molecular analyses of unrelated Charcot-Marie-Tooth disease patients suggest a high frequency of the CMT1A duplication. Am. J. hum. Genet. 53, 853–863 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Pentao, L., Wise, C.A., Chinault, A.C., Patel, P.I. & Lupski, J.R. Charcot-Marie-Tooth type 1A tandem duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet. 2, 292–300 (1992).

    CAS  Article  Google Scholar 

  15. 15

    Patel, P.I. et al. The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 159–165 (1992).

    CAS  Article  Google Scholar 

  16. 16

    Valentijn, L.J. et al. The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 166–170 (1992).

    CAS  Article  Google Scholar 

  17. 17

    Timmerman, V. et al. The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication. Nature Genet. 1, 171–175 (1992).

    CAS  Article  Google Scholar 

  18. 18

    Matsunami, N. et al. Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A. Nature Genet. 1, 176–179 (1992).

    CAS  Article  Google Scholar 

  19. 19

    Lupski, J.R. et al. Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 29–33 (1992).

    CAS  Article  Google Scholar 

  20. 20

    Chance, P.F. et al. Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: Evidence for gene dosage as a mechanism in CMT1A. Neurology 42, 2295–2299 (1992).

    CAS  Article  Google Scholar 

  21. 21

    Upadhyaya, M. et al. Charcot-Marie-Tooth disease 1A (CMT1A) associated with a maternal duplication of chromosome 17p11.2-12. Hum. Genet. 91, 392–394 (1993).

    CAS  Article  Google Scholar 

  22. 22

    Valentijn, L.J. et al. Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1 A. Nature Genet. 2, 288–291 (1992).

    CAS  Article  Google Scholar 

  23. 23

    Roa, B.B. et al. Charcot-Marie-Tooth disease type 1A: association with a spontaneous point mutation in the PMP22 gene. New Engl. J. Med. 329, 96–101 (1993).

    CAS  Article  Google Scholar 

  24. 24

    Dyck, P.J. Histologic measurements and fine structure of biopsied sural nerve: normal, and in peroneal muscular atrophy, hypertrophic neuropathy, and congenital sensory neuropathy. Mayo Clin. Proc. 41, 742–774 (1966).

    CAS  PubMed  Google Scholar 

  25. 25

    Edwards, A., Civitello, A., Hammond, H.A. & Caskey, C.T. DNA typing and genetic mapping with trimeric and tetrameric tandem repeats. Am. J. hum. Genet. 49, 746–756 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Edwards, A., Hammond, H.A., Jin, L., Caskey, C.T. & Chakraborty, R. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics 12, 241–253 (1992).

    CAS  Article  Google Scholar 

  27. 27

    Snipes, G.J., Suter, U., Welcher, A.A. & Shooter, E.M. Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J. cell. Biol. 117, 225–238 (1992).

    CAS  Article  Google Scholar 

  28. 28

    Roa, B.B. et al. Evidence for a recessive PMP22 point mutation in Charcot-Marie-Tooth disease type 1A. Nature Genet. 5, 189–194 (1993).

    CAS  Article  Google Scholar 

  29. 29

    Suter, U. et al. Trembler mouse carries a point mutation in a myelin gene. Nature 356, 241–244 (1992).

    CAS  Article  Google Scholar 

  30. 30

    Suter, U. et al. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc. natn. Acad. Sci. U.S.A. 89, 4382–4386 (1992).

    CAS  Article  Google Scholar 

  31. 31

    Lupski, J.R. & Garcia, C.A. Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A. Brain Path. 2, 337–349 (1992).

    CAS  Article  Google Scholar 

  32. 32

    Kaku, D.A., Parry, G.J., Malamut, R., Lupski, J.R. & Garcia, C.A. Nerve conduction studies in Charcot-Marie-Tooth polyneuropathy associated with a segmental duplication of chromosome 17. Neurology 43, 1806–1808 (1993).

    CAS  Article  Google Scholar 

  33. 33

    Hoogendijk, J.E. et al. Allelic heterogeneity in hereditary motor and sensory neuropathy type Ia (Charcot-Marie-Tooth disease type 1a). Neurology 43, 1010–1015 (1993).

    CAS  Article  Google Scholar 

  34. 34

    Killian, J.M. & Kloepfer, H.W. Homozygous expression of a dominant gene for Charcot-Marie-Tooth neuropathy. Ann. Neurol. 5, 515–522 (1979).

    CAS  Article  Google Scholar 

  35. 35

    Chance, P.F. et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72, 143–151 (1993).

    CAS  Article  Google Scholar 

  36. 36

    Byers, P.H. in The Metabolic Basis of Inherited Disease (eds Scriver, C.R. et al.) 2805–2842 (McGraw-Hill, New York, 1989).

    Google Scholar 

  37. 37

    Cohn, D.H., Starman, B.J., Blumberg, B. & Byers, P.H. Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1). Am. J. hum. Genet. 46, 591–601 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Bordo, D. & Argos, P. Suggestions for “safe” residue substitutions in site-directed mutagenesis. J. mol. Biol. 217, 721–729 (1991).

    CAS  Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Roa, B., Dyck, P., Marks, H. et al. Dejerine–Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet 5, 269–273 (1993).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing