BMC Medical Genetics (2007-11-01)

CADASIL in Arabs: clinical and genetic findings

  • AlSous M Walid,
  • AlKhairallah Thamer,
  • Alreshaid Abdulrahman,
  • Edris Abdulrahman,
  • Al Shubili Asmahan,
  • Bohlega Saeed,
  • Farah Samir,
  • Abu-Amero Khaled K

DOI
https://doi.org/10.1186/1471-2350-8-67
Journal volume & issue
Vol. 8, no. 1
p. 67

Abstract

Read online

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs. Methods We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL. Results The mean age of onset was 31 ± 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 ± 11. All NOTCH3 exons were screened for mutations, which revealed the presence of previously reported mutations c.406C>T (p.Arg110>Cys) in two families (family A&B) and c.475C>T (p.Arg133>Cys) mutation in family C. Conclusion CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups.