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A case of mild CADASIL patient with a novel heterozygous NOTCH3 variant

  • Choi, WooChan (Department of Neurology, Kyungpook National University Hospital) ;
  • Hwang, Yang-Ha (Department of Neurology, Kyungpook National University Hospital) ;
  • Lee, Jong-Mok (Department of Neurology, Kyungpook National University Hospital)
  • Received : 2021.11.05
  • Accepted : 2021.12.05
  • Published : 2022.06.30

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease caused by mutations in the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The spectrum of clinical manifestations is broad, ranging from asymptomatic to typical ischemic stroke, and mainly depends on the location of the mutations. We describe the case of a 76-year-old female without apparent neurological deficits. However, brain magnetic resonance imaging revealed confluent lesions in the white matter. Direct sequencing of the NOTCH3 gene revealed a novel pathogenic mutation, c.811T>A, which results in a mild phenotype. Therefore, this report will expand the current knowledge in regards to the mutations that can cause CADASIL.

Keywords

References

  1. Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, et al. Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant. Genet Med 2019;21:1895. https://doi.org/10.1038/s41436-018-0306-z
  2. Wang T, Baron M, Trump D. An overview of Notch3 function in vascular smooth muscle cells. Prog Biophys Mol Biol 2008;96:499-509. https://doi.org/10.1016/j.pbiomolbio.2007.07.006
  3. Tikka S, Baumann M, Siitonen M, Pasanen P, Poyhonen M, Myllykangas L, et al. CADASIL and CARASIL. Brain Pathol 2014;24:525-44. https://doi.org/10.1111/bpa.12181
  4. Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssiere C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997;350:1511-5. https://doi.org/10.1016/S0140-6736(97)08083-5
  5. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24. https://doi.org/10.1038/gim.2015.30
  6. Au KM, Li HL, Sheng B, Chow TC, Chen ML, Lee KC, et al. A novel mutation (C271F) in the Notch3 gene in a Chinese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Clin Chim Acta 2007;376:229-32. https://doi.org/10.1016/j.cca.2006.07.022
  7. Mukai M, Mizuta I, Watanabe-Hosomi A, Koizumi T, Matsuura J, Hamano A, et al. Genotype-phenotype correlations and effect of mutation location in Japanese CADASIL patients. J Hum Genet 2020;65:637-46. https://doi.org/10.1038/s10038-020-0751-9
  8. Hu Y, Sun Q, Zhou Y, Yi F, Tang H, Yao L, et al. NOTCH3 variants and genotype-phenotype features in Chinese CADASIL patients. Front Genet 2021;12:705284. https://doi.org/10.3389/fgene.2021.705284
  9. Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke 2010;41:630-4. https://doi.org/10.1161/strokeaha.109.568402
  10. Gravesteijn G, Hack RJ, Opstal AMV, van Eijsden BJ, Middelkoop HAM, Rodriguez Girondo MDM, et al. Eighteen-year disease progression and survival in CADASIL. J Stroke 2021;23:132-4. https://doi.org/10.5853/jos.2020.04112
  11. O'Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 2001;56:628-34. https://doi.org/10.1212/WNL.56.5.628
  12. Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology 2002;59:1134-8. https://doi.org/10.1212/WNL.59.8.1134