HLA in Narcolepsy in France

  • M. Billiard
  • J. Seignalet
  • H. Betuel
  • A. Marcadet
  • L. Gebuhrel
  • A. C. Freidel
  • C. Confavreux
  • A. Besset
  • J. Cadilhac


The genetic aspect of narcolepsy in man has long been considered, with the first report of a positive family history of narcolepsy made by Westphal (1877) even before the term “narcolepsy” was coined by Gelineau (1880). Since then a number of series have been published showing variable rates of probands with a positive family history of narcolepsy and suggesting either an autosomal dominant mode of inheritance with incomplete penetrance (Krabbe and Magnussen 1942; Daly and Yoss 1959; Baraitser and Parkes 1978) or a two-threshold multifactorial system (Nevsimalova-Bruhova and Roth 1972; Kessler 1976; Honda et al. 1983 a).


Depression Recombination Agarose Electrophoresis Neurol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andreas-Zietz A, Keller E, Scholz S, Albert ED, Roth B, Nevsimalova S, Sonka K, Docekal P, Ivaskova E, Schulz H, Geisler P (1986) DR2-negative narcolepsy. Lancet 2: 684–685PubMedCrossRefGoogle Scholar
  2. Baraitser M, Parkes JD (1978) Genetic study of narcoleptic syndrome. J Med Genet 15: 254–259PubMedCrossRefGoogle Scholar
  3. Betuel H, Gebuhrer L, Lambert J, Freidel AC, Farre A (1983) A possible new HLA-DR allele. Hum Immunol 8: 227–238PubMedCrossRefGoogle Scholar
  4. Billiard M, Seignalet J (1985) Extraordinary association between HLA-DR2 and narcolepsy. Lancet 1:226–227CrossRefGoogle Scholar
  5. Bonduelle M, Degos C (1976) Symptomatic narcolepsies: a critical study. In: Guilleminault C, Dement WC, Passouant P (eds) Narcolepsy. Spectrum, New York, pp 313–332Google Scholar
  6. Cohen D, Paul P, Font MP, Cohen O, Sayagh B, Marcadet A, Busson M, Mahouy G, Cann HM, Dausset J (1983) Analysis of HLA class I genes with restriction endonuclease fragments: implications for polymorphism of the human major histocompatibility complex. Proc Natl Acad Sci USA 80: 6289–6292PubMedCrossRefGoogle Scholar
  7. Cohen D, Le Gall I, Marcadet A, Font MP, Lalouel JM, Dausset J (1984) Clusters of HLA class II beta restriction fragments describe allelic series. Proc Natl Acad Sci USA 81: 7870–7874PubMedCrossRefGoogle Scholar
  8. Confavreux C, Gebuhrer L, Betuel H, Freidel C, Bastuji H, Aimard G, Devic M, Jouvet M (1987) HLA-DR2 negative narcolepsy. J Neurol Neurosurg Psychiatry 50: 635–636PubMedCrossRefGoogle Scholar
  9. Daly DD, Yoss RE (1959) A family with narcolepsy. Proc Staff Meet Mayo Clin 34: 313–320PubMedGoogle Scholar
  10. Day NE, Simons MJ (1976) Disease susceptibility genes — their identification by multiple case family studies. Tissue Antigens 8: 109–119PubMedGoogle Scholar
  11. Gelineau J (1880) De la narcolepsie. Gaz Hop (Paris) 53: 626–628;Google Scholar
  12. Gelineau J (1880) De la narcolepsie. Gaz Hop (Paris) 54: 635–637Google Scholar
  13. Guilleminault C (1986) Narcolepsy. Sleep 2: 99–101Google Scholar
  14. Honda Y, Asaka A, Tanimura M, Furusho T (1983 a) A genetic study of narcolepsy and excessive daytime sleepiness in 308 families with a narcolepsy or hypersomnia proband. In: Guilleminault C, Lugaresi E (eds) Sleep/wake disorders: natural history, epidemiology, and long-term evolution. Raven, New York, pp 187–199Google Scholar
  15. Honda Y, Asaka A, Tanaka Y, Juji T (1983 b) Discrimination of narcoleptic patients by using genetic markers and HLA. Sleep Res 12: 254Google Scholar
  16. Honda Y, Doi Y, Ninomiya R, Ninomiya C (1986) Increased frequency of non-insulin dependent diabetes mellitus among narcoleptic patients. Sleep 9: 254–259PubMedGoogle Scholar
  17. Inoko H, Ando A, Tsuji K, Matsuki K, Juji T, Honda Y (1986) HLA-DQ beta chain DNA restriction fragments can differentiate between healthy and narcoleptic individuals with HLA-DR2. Immunogenetics 23: 126–128PubMedCrossRefGoogle Scholar
  18. Juji T, Satake M, Honda Y, Doi Y (1984) HLA antigens in Japanese patients with narcolepsy. Tissue Antigens 24: 316–319PubMedCrossRefGoogle Scholar
  19. Kessler S (1976) Genetic factors in narcolepsy. In: Guilleminault C, Dement WC, Passouant P (eds) Narcolepsy. Spectrum, New York, 285–302Google Scholar
  20. Krabbe E, Magnussen G (1942) Familial narcolepsy. Acta Psychiatr Neurol 17: 149–173CrossRefGoogle Scholar
  21. Langdon N, Welsh KI, Van Dam M, Vaughan RW, Parkes JD (1984) Genetic markers in narcolepsy. Lancet 2: 1178–1180PubMedCrossRefGoogle Scholar
  22. Langdon N, Lock C, Welsh KI, Vergani D, Dorow R, Wachtel H, Palenschat D, Parkes JD (1986) Immune factors in narcolepsy. Sleep 9: 143–148PubMedGoogle Scholar
  23. Larhammar D, Schenning L, Gustaffson K, Wiman K, Claesson L, Rask L, Peterson PA (1982) Complete amino-acid sequence from an HLA-DR antigen-like β chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, B, and C antigens. Proc Natl Acad Sci USA 79: 3687–3691PubMedCrossRefGoogle Scholar
  24. Lascelles RG, Mohr PD, Peart I (1976) Unilateral cataplexy associated with systemic lupus erythematosus. J Neurol Neurosurg Psychiatr 39: 1023–1026PubMedCrossRefGoogle Scholar
  25. Marcadet A, Gebuhrer L, Betuel H, Seignalet J, Freidel AC, Confavreux C, Billiard M, Dausset J, Cohen D (1985) DNA polymorphism related to HLA-DR2 Dw2 in patients with narcolepsy. Immunogenetics 22: 679–683PubMedCrossRefGoogle Scholar
  26. Nevsimalova-Bruhova S, Roth B (1972) Heredofamilial aspects of narcolepsy and hypersomnia. Schweiz Arch Neurol Neurochir Psychiatr 110: 45–54PubMedGoogle Scholar
  27. Neely SE, Rosenberg RS, Spire JP, Antel J, Arnason BGW (1986) HLA antigens in narcolepsy. Neurology 36 [Suppl 1]: 299Google Scholar
  28. Parkes JD, Langdon N. Lock C (1986) Narcolepsy and immunity. Br Med J 292: 359–360CrossRefGoogle Scholar
  29. Poirer G, Montplaisir J, Decary F, Momege D, Lebrun A (1986) HLA antigens in narcolepsy and idiopathic nervous system hypersomnolence. Sleep 9: 153–158Google Scholar
  30. Seignalet J (1980) Recherche d’anticorps anti-cellules B et typage HLA-DR à Montpellier. Rev Fr Transfus 23: 411–425Google Scholar
  31. Seignalet J, Billiard M (1984) Possible association between HLA-B7 and narcolepsy. Tissue Antigens 23: 188–189PubMedCrossRefGoogle Scholar
  32. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98, 503–517PubMedCrossRefGoogle Scholar
  33. Stein M, Keller SE, Schleifer SJ (1985) Stress and immunomodulation: the role of depression and neuroendocrine function. J Immunol 135 [Suppl 2]: 827s–833sPubMedGoogle Scholar
  34. Thomson G (1985) The mode of inheritance of the HLA-linked gene predisposing to narcolepsy. Tissue Antigens 26: 201–203PubMedCrossRefGoogle Scholar
  35. Westphal C (1877) Eigentümliche mit Einschlafen verbundene Anfalle. Arch Psychiatr Nervenkr 7: 631–635Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • M. Billiard
  • J. Seignalet
  • H. Betuel
  • A. Marcadet
  • L. Gebuhrel
  • A. C. Freidel
  • C. Confavreux
  • A. Besset
  • J. Cadilhac

There are no affiliations available

Personalised recommendations