Additive effect of nuclear and mitochondrial mutations in a patient with mitochondrial encephalomyopathy.
We describe the case of a woman in whom combination of a mitochondrial (MT-CYB) and a nuclear (SDHB) mutation was associated with clinical and metabolic features suggestive of a mitochondrial disorder. The mutations impaired overall energy metabolism in the patient's muscle and fibroblasts and increased cellular susceptibility to oxidative stress. To clarify the contribution of each mutation to the phenotype, mutant yeast strains were generated. A significant defect in strains carrying the Sdh2 mutation, either alone or in combination with the cytb variant, was observed. Our data suggest that the SDHB mutation was causative of the mitochondrial disorder in our patient with a possible cumulative contribution of the MT-CYB variant. To our knowledge, this is the first association of bi-genomic variants in the mtDNA and in a nuclear gene encoding a subunit of complex II.
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Claudia
C
Nesti
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Maria Chiara
MC
Meschini
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Brigitte
B
Meunier
Metabolic and Neuromuscular Unit, AOU Meyer Hospital, Florence, Italy.
Michele
M
Sacchini
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Stefano
S
Doccini
Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Alessandro
A
Romano
Unit for Neuromuscular and Neurodegenerative Diseases, "Bambino Gesù" Children's Hospital, Rome, Italy and.
Sara
S
Petrillo
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Ilaria
I
Pezzini
Laboratoire de Chimie Bactérienne, CNRS, 31 ch. J. Aiguier, 13402 Marseilles, France.
Nadir
N
Seddiki
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
Anna
A
Rubegni
Unit for Neuromuscular and Neurodegenerative Diseases, "Bambino Gesù" Children's Hospital, Rome, Italy and.
Fiorella
F
Piemonte
Metabolic and Neuromuscular Unit, AOU Meyer Hospital, Florence, Italy.
M Alice
MA
Donati
Laboratoire de Chimie Bactérienne, CNRS, 31 ch. J. Aiguier, 13402 Marseilles, France.
Gael
G
Brasseur
Molecular Medicine, IRCCS Stella Maris, Pisa, Italy filippo3364@gmail.com.
Filippo M
FM
Santorelli
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis* / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length; D012441:Saccharomyces cerevisiae
D000255:Adenosine Triphosphate