Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction

Valerio Carelli, Carla Giordano, Giulia D'Amati

Research output: Contribution to journalArticlepeer-review

Abstract

Here we define a category of human, maternally inherited disorders that are characterized by a homoplasmic mtDNA pathogenic mutation with variable penetrance and a stereotypical clinical expression, usually restricted to a single tissue. Examples of such disorders include Leber's hereditary optic neuropathy, mitochondrial non-syndromic sensorineural hearing loss, and a form of mitochondrial hypertrophic cardiomyopathy. The mtDNA mutation is necessary, but not sufficient to induce the pathology, and multiple lines of evidence suggest a two-locus genetic model involving a primary mitochondrial mutation and a nuclear modifier. The nuclear modifier does not induce any pathology per se, but it contributes to the pathogenic effect of the mitochondrial mutation. The nuclear modifier could be a common functional polymorphism in a tissue-specific protein, possibly with mitochondrial location.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalTrends in Genetics
Volume19
Issue number5
DOIs
Publication statusPublished - May 1 2003

ASJC Scopus subject areas

  • Genetics

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