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 Pala & 4 others Alessandro Achilli, Anna Olivieri, Antonio Torroni, Valerio Carelli

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages954-958
Number of pages5
JournalHuman Mutation
Volume35
Issue number8
Early online date28 Jun 2014
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Fingerprint

Mitochondrial DNA
Retinal Dystrophies
Exercise
Cytochromes b
Electron Transport Complex III
Deafness
Muscular Diseases
Deglutition Disorders
Gait
Base Pairing
Cataract
Embryonic Development
Epithelium
Nucleotides
Mothers
Amino Acids
Genes
Proteins

Cite this

Carossa, V., Ghelli, A., Tropeano, C. V., Valentino, M. L., Iommarini, L., Maresca, A., ... Carelli, V. (2014). A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance. Human Mutation, 35(8), 954-958. https://doi.org/10.1002/humu.22596
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 ; Tonon, Caterina ; Lodi, Raffaele ; Martinuzzi, Andrea ; De Nardo, Vera ; Rugolo, Michela ; Ferretti, Luca ; Gandini, Francesca ; Pala, Maria ; Achilli, Alessandro ; Olivieri, Anna ; Torroni, Antonio ; Carelli, Valerio. / A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance. In: Human Mutation. 2014 ; Vol. 35, No. 8. pp. 954-958.
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abstract = "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.",
keywords = "Cybrid, Exercise intolerance, MT-CYB, MtDNA, Multi system mitochondrial disease",
author = "Valeria Carossa and Anna Ghelli and Tropeano, {Concetta Valentina} and Valentino, {Maria Lucia} and Luisa Iommarini and Alessandra Maresca and Leonardo Caporali and {La Morgia}, Chiara and Rocco Liguori and Piero Barboni and Michele Carbonelli and Giovanni Rizzo and Caterina Tonon and Raffaele Lodi and Andrea Martinuzzi and {De Nardo}, Vera and Michela Rugolo and Luca Ferretti and Francesca Gandini and Maria Pala and Alessandro Achilli and Anna Olivieri and Antonio Torroni and Valerio Carelli",
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Carossa, V, Ghelli, A, Tropeano, CV, Valentino, ML, Iommarini, L, Maresca, A, Caporali, L, La Morgia, C, Liguori, R, Barboni, P, Carbonelli, M, Rizzo, G, Tonon, C, Lodi, R, Martinuzzi, A, De Nardo, V, Rugolo, M, Ferretti, L, Gandini, F, Pala, M, Achilli, A, Olivieri, A, Torroni, A & Carelli, V 2014, 'A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance', Human Mutation, vol. 35, no. 8, pp. 954-958. https://doi.org/10.1002/humu.22596

A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance. / 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; Tonon, Caterina; Lodi, Raffaele; Martinuzzi, Andrea; De Nardo, Vera; Rugolo, Michela; Ferretti, Luca; Gandini, Francesca; Pala, Maria; Achilli, Alessandro; Olivieri, Anna; Torroni, Antonio; Carelli, Valerio.

In: Human Mutation, Vol. 35, No. 8, 08.2014, p. 954-958.

Research output: Contribution to journalArticle

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T1 - A Novel in-Frame 18-bp Microdeletion in MT-CYB Causes a Multisystem Disorder with Prominent Exercise Intolerance

AU - Carossa, Valeria

AU - Ghelli, Anna

AU - Tropeano, Concetta Valentina

AU - Valentino, Maria Lucia

AU - Iommarini, Luisa

AU - Maresca, Alessandra

AU - Caporali, Leonardo

AU - La Morgia, Chiara

AU - Liguori, Rocco

AU - Barboni, Piero

AU - Carbonelli, Michele

AU - Rizzo, Giovanni

AU - Tonon, Caterina

AU - Lodi, Raffaele

AU - Martinuzzi, Andrea

AU - De Nardo, Vera

AU - Rugolo, Michela

AU - Ferretti, Luca

AU - Gandini, Francesca

AU - Pala, Maria

AU - Achilli, Alessandro

AU - Olivieri, Anna

AU - Torroni, Antonio

AU - Carelli, Valerio

N1 - No full text in Eprints. HN 16/11/2017

PY - 2014/8

Y1 - 2014/8

N2 - 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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KW - Cybrid

KW - Exercise intolerance

KW - MT-CYB

KW - MtDNA

KW - Multi system mitochondrial disease

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