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A Novel in‐Frame 18‐bp Microdeletion in MT ‐ CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance
Author(s) -
Carossa Valeria,
Ghelli Anna,
Tropeano Concetta Valentina,
Valentino Maria Lucia,
Iommarini Luisa,
Maresca Alessandra,
Caporali Leonardo,
La Morgia Chiara,
Liguori Rocco,
Barboni Piero,
Carbonelli Michele,
Rizzo Giovanni,
To Caterina,
Lodi Raffaele,
Martinuzzi Andrea,
Nardo Vera,
Rugolo Michela,
Ferretti Luca,
Gandini Francesca,
Pala Maria,
Achilli Alessandro,
Olivieri Anna,
Torroni Antonio,
Carelli Valerio
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22596
Subject(s) - heteroplasmy , exercise intolerance , biology , genetics , mitochondrial dna , stop codon , myopathy , cytochrome b , mitochondrial myopathy , gene , medicine , heart failure
A novel heteroplasmic mitochondrial DNA (mt DNA ) 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 mt DNA 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.