Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): first description of a Russian family with the identified mutation in the Notch3 gene


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Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial form of ischemic stroke caused by mutations in the Notch3 gene on chromosome 19q12. Clinically, CADASIL develops as a cerebrovascular ‘small vessel disease’: against a background of repeated lacunar strokes, progressing are subcortical, pseudobulbar and cerebellar syndromes and cognitive decline. Neuroimaging methods (CT, MRI) reveal combination of small lacunar infarcts of variable location with diffuse white matter changes (leucoaraosis). In this paper we present the first description of a Russian family with the verified mutation in the Notch3 gene, nucleotide change 832G>A in exon 5 leading to substitution of valine to methionine (Val252Met) at protein codon 252. This missense mutation is novel and has not been reported before in other families with CADASIL syndrome. The observation presented confirms that CADASIL syndrome should be suspected in all cases of white matter disease of unknown origin.

 
 

About the authors

S. N. Illarioshkin

Research Center of Neurology, Russian Academy of Medical Sciences, Moscow

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

P. A. Slominsky

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow

Email: platonova@neurology.ru
Russian Federation

M. I. Shadrina

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow

Email: platonova@neurology.ru
Russian Federation

M. V. Partola

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow

Email: platonova@neurology.ru
Russian Federation

D. V. Kandyba

Saint-Petersburg Medical Academy of Postgraduate Education, Saint-Petersburg

Email: platonova@neurology.ru
Russian Federation

N. M. Zhulev

Saint-Petersburg Medical Academy of Postgraduate Education, Saint-Petersburg

Email: platonova@neurology.ru
Russian Federation

References

  1. Буссер М.Г., Жутель А., Шабриа Х. и др. ЦАДАСИЛ – церебральная аутосомноодоминантная артериопатия с субкортикальными инфарктами и лейкоэнцефалопатией. Неврол. журн. 1997; 3: 20–25.
  2. Иллариошкин С.Н. Генетика сосудистых заболеваний мозга. В кн.: Суслина З.А. (ред.) Очерки ангионеврологии. М.: Атмосфера, 2005: 327–345.
  3. Калашникова Л.А. Неврологические аспекты сосудистой деменции. В кн.: Суслина З.А. (ред.) Очерки ангионеврологии. М.: Атмосфера, 2005: 277–288.
  4. Мозолевский Ю.В., Янакаева Т.А., Мельникова Е.А. и др. Церебральная аутосомно-доминантная артериопатия с субкортикальными инфарктами и лейкоэнцефалопатией. Неврол. журн. 2005; 2: 34–40.
  5. Baudrimont M., Dubas F., Joutel A. et al. Autosomal dominant leukoencephalopathy and subcortical ischemic strokes: a clinicopathological study. Stroke 1993; 24: 122–125.
  6. Bousser M.G., TournierrLasserve E., Aylward R. et al. Recurrent strokes in a family with diffuse white matter abnormalities and muscular lipidosis. A new mitochondrial cytopathy. J. Neurol. 1988; 235 (Suppl. 1): 54–55.
  7. Chabriat H., Joutel A., Vahedi K. et al. CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): clinical features and neuroimaging. Bull. Acad. Natl. Med. 2000; 184: 1523–1531.
  8. Davous P., FallettBianco C. Demence sous cortical familial avec leukoencephalopathy arteriopathic. Observation clinicopathologic. Rev. Neurol. 1991; 5: 376–384.
  9. Domenga V., Fardoux P., Lacombe P. et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev. 2004; 18: 2730–2735.
  10. Dubroca C., Lacombe P., Domenga V. et al. Impaired vascular mechanotransduction in a transgenic mouse model of CADASIL arteriopathy. Stroke 2005; 36: 113–117.
  11. Erkinjuntti T., Inzitari D., Pantoni L. et al. Research criteria for subcortical vascular dementia in clinical trials. J. Neural Transm. 2000; 59 (Suppl.): 23–30.
  12. Fukutake T., Hirayama K. Familial young adult onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension. Eur. Neurol. 1995; 35: 69–79.
  13. Joutel A., Corpechot C., Ducros A. et al. Notch3 mutations in CADASIL, a hereditary adult onset condition causing stroke and dementia. Nature 1996; 383; 707–710.
  14. Kalimo H., Ruchoux M., Viitanen M. et al. CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol. 2002; 12: 371–384.
  15. Kim Y., Choi E.J., Choi C.G. et al. Characteristics of CADASIL in Korea: a novel cysteine sparing Notch3 mutation. Neurology 2006; 66: 1511–1516.
  16. Lacombe P., Oligo C., Domenga V. et al. Impaired cerebral vasoreactivity in a transgenic mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2005; 36: 1053–1058.
  17. Maeda S., Nakayama H., Isaka K. et al. Familial unusual encephalopathy of Binswanger’s type without hypertension. Folia Psychiatr. Neurol. Jpn. 1976; 30: 165–177.
  18. Markus H.S. Genes for stroke. J. Neurol. Neurosurg. Psychiatry 2004; 75: 1229–1231.
  19. Markus H.S., Martin R.J., Simpson M.A. et al. Diagnostic strategies in CADASIL. Neurology 2002; 59: 1134–1138.
  20. Mayer M., Straube A., Bruening R. et al. Muscle and skin biopsies are a sensitive diagnostic tool in the diagnosis of CADASIL. J. Neurol. 1999; 246: 526–532.
  21. Peters N., Herzog J., Opherk C., Dichgans M. A two-year clinical follow-up study in 80 CADASIL subjects. Progression patterns and implications for clinical trials. Stroke 2004; 35: 1603–1608.
  22. Peters N., Holtmannspotter M., Opherk C. et al. Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology 2006; 66: 1517–1522.
  23. Roman G.C., Erkinjuntti T., Wallin A. et al. Subcortical ischemic vascular dementia. Lancet Neurol. 2002 ; 1: 426–436.
  24. Sonninen V., Savontaus M.L. Hereditary multiiinfarct dementia. Eur. Neurol. 1987; 27: 209–215.
  25. Stevens D.L., Hewlett R.H., Brownell B. Chronic familial vascular encephalopathy. Lancet 1977; 2: 1364–1365.
  26. TournierrLasserve E., IbaaZizen M..T., Romero N. et al. Autosomal dominant syndrome with stroke like episodes and leukoencephalopathy. Stroke 1991; 22: 1297–1302.
  27. van Bogaert L. Encephalopathie sous cortical progressive (Binswanger) a evolution rapide chez deux soeurs. Med. Hellen. 1955; 24: 961–972.
  28. van den Boom R., Lesnik Oberstein S.A.J., Ferrari M.D. et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages – 3rdd6th decades. Radiology 2003; 229: 683–690.
  29. Viswanathan A., Gschwendtner A., Guichard J..P. et al. Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 2007; 69: 172–179.

Copyright (c) 2008 Illarioshkin S.N., Slominsky P.A., Shadrina M.I., Partola M.V., Kandyba D.V., Zhulev N.M.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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