Disease-related versus polymorphic mutations in human mitochondrial tRNAs: Where is the difference?

AUTOR(ES)

Florentz, Catherine

FONTE

Oxford University Press

RESUMO

A number of point mutations in human mitochondrial (mt) tRNA genes are correlated with a variety of neuromuscular and other severe disorders including encephalopathies, myopathies, cardiopathies and diabetes. The complexity of the genotype/phenotype relationships, the diversity of possible molecular impacts of the different mutations at the tRNA structure/function levels, and the exponential discovery of new mutations call for the search for unifying features. Here, the basic features (at the levels of primary and secondary structure) of 68 ‘pathogenic’ mutations are compared with those of 64 ‘polymorphic’ neutral mutations, revealing that these standard parameters for mutant analysis are not sufficient to predict the pathogenicity of mt tRNA mutations. Thus, case by case molecular investigation remains the only means of assessing the growing family of pathogenic mutations in mt tRNAs. New lines of research are suggested.

Documentos Relacionados

• Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus.
• The mitochondrial calcium uniporter: a new therapeutic target for Parkinson’s disease-related cardiac dysfunctions?
• Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases
• Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction.
• Cell surface expression of the Alzheimer disease-related presenilin proteins