TY - JOUR
T1 - Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction
AU - Carelli, Valerio
AU - Giordano, Carla
AU - D'Amati, Giulia
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0168-9525(03)00072-6
DO - 10.1016/S0168-9525(03)00072-6
M3 - Article
C2 - 12711217
AN - SCOPUS:0037406049
VL - 19
SP - 257
EP - 262
JO - Trends in Genetics
JF - Trends in Genetics
SN - 0168-9525
IS - 5
ER -