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Cracking the nuclear‐mitochondrial code in Leber hereditary optic neuropathy
Author(s) -
Carelli V.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.03171
Subject(s) - mitochondrial dna , penetrance , genetics , nuclear gene , biology , leber's hereditary optic neuropathy , mitochondrial disease , haplotype , optic neuropathy , mitochondrion , genome , mutation , nuclear dna , disease , computational biology , bioinformatics , gene , allele , medicine , neuroscience , phenotype , pathology , optic nerve
Summary Leber hereditary optic neuropathy ( LHON ) is primarily determined by mt DNA pathogenic mutations affecting complex I that are necessary but not sufficient to express the disease. In fact, there remain incomplete penetrance and male prevalence for which it is assumed that further complex genetic, anatomical and environmental interactions are necessary to trigger the neurodegenerative process. On the genetic ground, besides the primary mt DNA mutations there are further determinants, like the mt DNA copy number and the mt DNA background variability (haplotype) that are certainly relevant. However, variability of the nuclear genome is also assumed to play a relevant modifying role. Currently, multi‐layered strategies are employed to crack this nuclear‐mitochondrial code to finally reach a complete understanding of the genetic basis of LHON . The combination of next generation sequencing approaches, expression and metabolic profiles, and functional studies of neuronal tissue generated from patient‐derived reprogrammed stem cells casts hope to shed light on the genetic basis and pathogenic mechanisms in LHON , ultimately leading to the development of targeted therapeutic strategies.