Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia

  • Tsun Haw Toh Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Kheng Seang Lim Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Ching Ching Ng Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
  • Imran Idris Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Sherrini Bazir Ahmad Subang Jaya Medical Centre, Kuala Lumpur, Malaysia.
  • Thien Thien Lim Division of Neurology, Island Hospital, Penang, Malaysia.
  • Irene Looi Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia.
  • Ai Huey Tan Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Chung Kin Chan Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
  • Chun Shen Lim Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
  • Chong Tin Tan Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Keywords: CADASIL, Malaysia, R544C

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small cerebral arteries. This case series aims to describe the mutations in NOTCH3 and their phenotypes in Malaysia. We included patients who were genetically confirmed to have CADASIL, diagnosed at the University of Malaya Medical Centre, Malaysia. Family members who fulfilled clinical or imaging criteria, and patients from two previous published Malaysian families were also included. Six families (eleven cases) were included in this series. Genetic testing revealed NOTCH3 mutations in c.328C>T (p.Arg110Cys, R110C), c.533T>G (p.Cys185Gly, C185G), c.1630C>T (p.Arg544Cys, R544C) and c.160C>T (p.Arg54Cys, R54C). Two out of four Chinese families had R544C mutation in exon 11, with a later age of onset, absence of migraine and lack of anterior temporal pole involvement on MRI. One family with mixed Indian and Chinese ancestry had a mutation in exon 3 with R110C and another Indian family exon 4 with C185G mutation. This case series highlights the genotypic and phenotypic variability of CADASIL in a multiethnic country. The finding of p.Arg544Cys mutation among the older Chinese families, similar to those reported in Jeju Island and Taiwan, suggest the need to screen the older Chinese stroke patients with typical MRI changes.

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Published
2019-08-17
How to Cite
Toh, T. H., Lim, K. S., Ng, C. C., Idris, I., Ahmad, S. B., Lim, T. T., Looi, I., Tan, A. H., Chan, C. K., Lim, C. S. and Tan, C. T. (2019) “Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia”, Neuroscience Research Notes, 2(3), pp. 1-11. doi: 10.31117/neuroscirn.v2i3.35.
Section
Research Notes