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; Alessandro Achilli; Anna Olivieri; Antonio Torroni; Valerio Carelli

doi:10.1002/humu.22596

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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38 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.

Original language	English
Pages (from-to)	954-958
Number of pages	5
Journal	Human Mutation
Volume	35
Issue number	8
Early online date	28 Jun 2014
DOIs	https://doi.org/10.1002/humu.22596
Publication status	Published - 1 Aug 2014
Externally published	Yes

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Carossa, V., Ghelli, A., Tropeano, C. V., Valentino, M. L., 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., ... 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

@article{a08c7f51b8ce4851973c288e93f317d3,

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

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",

note = "No full text in Eprints. HN 16/11/2017",

year = "2014",

month = aug,

day = "1",

doi = "10.1002/humu.22596",

language = "English",

volume = "35",

pages = "954--958",

journal = "Human Mutation",

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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

TY - JOUR

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 - 2014/8/1

Y1 - 2014/8/1

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.

AB - 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.

KW - Cybrid

KW - Exercise intolerance

KW - MT-CYB

KW - MtDNA

KW - Multi system mitochondrial disease

UR - http://www.scopus.com/inward/record.url?scp=84904408815&partnerID=8YFLogxK

U2 - 10.1002/humu.22596

DO - 10.1002/humu.22596

M3 - Article

C2 - 24863938

AN - SCOPUS:84904408815

VL - 35

SP - 954

EP - 958

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 8

ER -

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

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