Format

Send to

Choose Destination
See comment in PubMed Commons below
Hum Mutat. 2011 Nov;32(11):1319-25. doi: 10.1002/humu.21575. Epub 2011 Sep 19.

A comparative analysis approach to determining the pathogenicity of mitochondrial tRNA mutations.

Author information

1
Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, UK.

Abstract

Distinguishing pathogenic from polymorphic changes poses significant problems for geneticists and despite 30 years of postgenomic experience this remains the case in mitochondrial genetics. Base substitutions in mitochondrial tRNA (mt-tRNA) genes are particularly difficult, but important, because they are common causes of pathology and associated with high rates of transmission. Providing accurate genetic advice to patients and their families is of paramount importance in disease prevention, and brings into sharp focus the factors used to distinguish pathogenic from polymorphic variants. We have reevaluated our pathogenicity scoring system for mt-tRNA mutations following a considerable increase in the number reported since the system was devised in 2004. This allowed us to address notable issues including the underestimation of "definitely pathogenic" mutations resulting from insufficient data collection. We illustrate the robustness of our revised scoring system using novel pathogenic and previously reported polymorphic changes and conclude that while clear evidence from single-fiber and/or trans-mitochondrial cybrid studies remains the gold standard for assigning pathogenicity, our scoring system is valuable for deciding which mt-tRNA mutations to investigate further using these labor-intensive techniques.

PMID:
21882289
DOI:
10.1002/humu.21575
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center