Human Mutation · 2014 · 43 citations · 18 references
Life SciencesGeneticsMolecular GeneticsMedical GeneticsMitochondrial BiologyMitochondrial GeneticsGenetic DisordersInborn Errors Of MetabolismMitochondrial DiseaseMitochondrial DisordersMitochondrial DysfunctionMuscular DystrophyComplex Iii FunctionGaitMitochondrial DeafnessMitochondrial Dna DeletionsMitochondrial Dna GeneticsMitochondrial Genome DeletionsMitochondrial MyopathiesMultisystem Mitochondrial Disease
A novel heteroplasmic mitochondrial DNA (mtDNA) microdeletion affecting the cytochrome b gene (MT-CYB) was identified in an Italian female patient with a multisystem disease characterized by sensorineural deafness, cataracts, retinal pigmentary dystrophy, dysphagia, postural and gait instability, and myopathy with prominent exercise intolerance. The deletion is 18-base pair long and encompasses nucleotide positions 15,649-15,666, causing the loss of six amino acids (Ile-Leu-Ala-Met-Ile-Pro) in the protein, but leaving the remaining of the MT-CYB sequence in frame. The defective complex III function was cotransferred with mutant mtDNA in cybrids, thus unequivocally establishing its pathogenic role. Maternal relatives failed to show detectable levels of the deletion in blood and urinary epithelium, suggesting a de novo mutational event. This is the second report of an in-frame intragenic deletion in MT-CYB, which most likely occurred in early stages of embryonic development, associated with a severe multisystem disorder with prominent exercise intolerance.
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Ian A. Trounce, Yoon L. Kim, Albert S. Jun et al. · Methods in enzymology on CD-ROM/Methods in enzymology · 1996 · 745 citations