The investigation and diagnosis of pathogenic mitochondrial DNA mutations in human urothelial cells.
Patients with mitochondrial DNA disease are amongst the most challenging to diagnose and manage given the striking phenotypic and genetic heterogeneity, which characterise these conditions. Recently, we and others have demonstrated the m.3243A>G mutation, one of the most common mitochondrial DNA pathogenic mutations, is present at clinically relevant levels in urinary epithelium, thus providing a practical, non-invasive test for diagnosis and mutation screening. In this study we further evaluate the use of these cells in detecting the m.3243A>G mutation, other mtDNA tRNA gene point mutations including the m.8344A>G mutation and single large-scale mtDNA deletions. We observe a robust relationship between m.3243A>G levels in urothelial cells and clinically affected tissues that does not change with time. Conversely, single large-scale mtDNA deletions can be detected in urothelial cells, with higher levels present in younger patients with more severe disease, but generally mtDNA deletion levels are not representative of those seen in a clinically affected tissue. Our results have implications for the diagnosis, management and counselling of families with mtDNA disease.
Blackwood
John K
JK
Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Whittaker
Roger G
RG
Blakely
Emma L
EL
Alston
Charlotte L
CL
Turnbull
Douglass M
DM
Taylor
Robert W
RW
D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005453:Fluorescence; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion; D019459:Urothelium
D004272:DNA, Mitochondrial