Absence of mtDNA mutations in leukocytes of CADASIL patients.
BACKGROUND
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.


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


RESULTS
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.


CONCLUSIONS
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.
Abu-Amero
Khaled K
KK
Mitochondrial Research Laboratory, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. abuamero@gmail.com
Hellani
Ali
A
Bohlega
Saeed
S