A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance

Valeria Carossa, Anna Ghelli, Concetta Valentina Tropeano, Maria Lucia Valentino, Luisa Iommarini, Alessandra Maresca, Leonardo Caporali, Chiara La Morgia, Rocco Liguori, Piero Barboni, Michele Carbonelli, Giovanni Rizzo, Caterina Tonon, Raffaele Lodi, Andrea Martinuzzi, Vera De Nardo, Michela Rugolo, Luca Ferretti, Francesca Gandini, Maria PalaAlessandro Achilli, Anna Olivieri, Antonio Torroni, Valerio Carelli

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34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)954-958
Number of pages5
JournalHuman Mutation
Issue number8
Early online date28 Jun 2014
Publication statusPublished - 1 Aug 2014
Externally publishedYes


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