Absence of mtDNA mutations in leukocytes of CADASIL patients

Ultrastructural and biochemical abnormalities of mitochondria have been reported in skeletal muscle biopsies of CADASIL patients with mutations in the NOTCH3 nuclear gene. Additionally, it was proposed that NOTCH3 gene mutations may predispose the mitochondrial DNA (mtDNA) to mutations.

We sequenced the entire mitochondrial genome in five Arab patients affected by CADASIL.

The mean number of mtDNA sequence variants (synonymous and nonsynonymous) in CADASIL patients was not statistically significantly different from that in controls (p = 0.378). After excluding haplogroup specific single nucleotide polymorphisms (SNPs) and proved silent polymorphisms, no known or novel pathologic mtDNA mutation(s) could be detected in any patient. Additionally, there was no difference in the prevalence of different mitochondrial haplogroups between patients and controls.

Our study group is too small for any valid conclusion to be made. However, if our observation is confirmed in larger study group, then mtDNA mutations or mitochondrial haplogroups may not be important in the pathogenesis of CADASIL.