What is a 'novel' mtDNA mutation--and does 'novelty' really matter?

BANDELT HJ; SALAS A; BRAVI CM

Journal of Human Genetics

Springer Japan

Año: 2007 vol. 51 p. 1073 - 1082

The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled bythe seeming novelty of mutations that are either nonsynonymous or affect theprotein synthesis machinery in patients. In order to determine the novelty of adetected mutation, the working geneticist nearly always consults MITOMAP--oftenexclusively. By reanalyzing some case studies of refractory anemia with ringsideroblasts, prostate cancer, and hearing impairment, we demonstrate that thepractice of solely relying on MITOMAP can be most misleading. A notoriousexample is the T1243C mutation, which was assessed to be novel and deemed to beassociated with some (rare) disease simply because researchers did not realizethat T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majorityof ´novel´ mutations suspected of being pathogenic are in actual fact known (andpresumably neutral) polymorphisms (although unknown to MITOMAP), and thisbecomes glaringly evident when proper database searches and straightforwardInternet queries are carried out.