20 years of human mtDNA pathologic point mutations: carefully reading the pathogenicity criteria.
Despite the strong purifying selection that occurs during embryonic development, the particular location and features of mitochondrial DNA make it especially susceptible to accumulating point mutations, giving rise to a large number of mitochondrial DNA variants. Many of these will have moderate or no phenotypic effects but others will be the cause of very dramatic diseases, usually known as mitochondriopathies. Because of the abundance of different mitochondrial DNA variants, it is not easy to determine whether a new mutation is pathogenic. To facilitate this task, different criteria have been proposed, but they are often either too severely or too loosely applied. Citing examples from the literature, in this paper we discuss some critical aspects of these criteria.
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain. jmontoya@unizar.es
Julio
J
Montoya
Ester
E
López-Gallardo
Carmen
C
Díez-Sánchez
Manuel J
MJ
López-Pérez
Eduardo
E
Ruiz-Pesini
D019943:Amino Acid Substitution; D002467:Cell Nucleus / Q000235:genetics / Q000502:physiology; D004269:DNA, Bacterial / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics; D017243:MERRF Syndrome / Q000235:genetics; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013559:Symbiosis
D004269:DNA, Bacterial; D004272:DNA, Mitochondrial