The COQ2 genotype predicts the severity of coenzyme Q10 deficiency

Maria Andrea Desbats, Valeria Morbidoni, Micol Silic-Benussi, Mara Doimo, Vincenzo Ciminale, Matteo Cassina, Sabrina Sacconi, Michio Hirano, Giuseppe Basso, Fabien Pierrel, Placido Navas, Leonardo Salviati, Eva Trevisson

Research output: Contribution to journalArticle

Abstract

COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.

Original languageEnglish
Pages (from-to)4256-4265
Number of pages10
JournalHuman Molecular Genetics
Volume25
Issue number19
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

coenzyme Q10
Genotype
Infant, Newborn, Diseases
Yeasts
Phenotype
Mutation
Brain Diseases
Mutant Proteins
Transferases
Mitochondria
Alleles
Enzymes
Genes
Coenzyme Q10 Deficiency
Proteins
4-hydroxybenzoic acid

Keywords

  • Journal Article

Cite this

The COQ2 genotype predicts the severity of coenzyme Q10 deficiency. / Desbats, Maria Andrea; Morbidoni, Valeria; Silic-Benussi, Micol; Doimo, Mara; Ciminale, Vincenzo; Cassina, Matteo; Sacconi, Sabrina; Hirano, Michio; Basso, Giuseppe; Pierrel, Fabien; Navas, Placido; Salviati, Leonardo; Trevisson, Eva.

In: Human Molecular Genetics, Vol. 25, No. 19, 01.10.2016, p. 4256-4265.

Research output: Contribution to journalArticle

Desbats, MA, Morbidoni, V, Silic-Benussi, M, Doimo, M, Ciminale, V, Cassina, M, Sacconi, S, Hirano, M, Basso, G, Pierrel, F, Navas, P, Salviati, L & Trevisson, E 2016, 'The COQ2 genotype predicts the severity of coenzyme Q10 deficiency', Human Molecular Genetics, vol. 25, no. 19, pp. 4256-4265. https://doi.org/10.1093/hmg/ddw257
Desbats, Maria Andrea ; Morbidoni, Valeria ; Silic-Benussi, Micol ; Doimo, Mara ; Ciminale, Vincenzo ; Cassina, Matteo ; Sacconi, Sabrina ; Hirano, Michio ; Basso, Giuseppe ; Pierrel, Fabien ; Navas, Placido ; Salviati, Leonardo ; Trevisson, Eva. / The COQ2 genotype predicts the severity of coenzyme Q10 deficiency. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 19. pp. 4256-4265.
@article{137b790140ca45f0a2764a8a0c33fe70,
title = "The COQ2 genotype predicts the severity of coenzyme Q10 deficiency",
abstract = "COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.",
keywords = "Journal Article",
author = "Desbats, {Maria Andrea} and Valeria Morbidoni and Micol Silic-Benussi and Mara Doimo and Vincenzo Ciminale and Matteo Cassina and Sabrina Sacconi and Michio Hirano and Giuseppe Basso and Fabien Pierrel and Placido Navas and Leonardo Salviati and Eva Trevisson",
note = "{\circledC} The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2016",
month = "10",
day = "1",
doi = "10.1093/hmg/ddw257",
language = "English",
volume = "25",
pages = "4256--4265",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "19",

}

TY - JOUR

T1 - The COQ2 genotype predicts the severity of coenzyme Q10 deficiency

AU - Desbats, Maria Andrea

AU - Morbidoni, Valeria

AU - Silic-Benussi, Micol

AU - Doimo, Mara

AU - Ciminale, Vincenzo

AU - Cassina, Matteo

AU - Sacconi, Sabrina

AU - Hirano, Michio

AU - Basso, Giuseppe

AU - Pierrel, Fabien

AU - Navas, Placido

AU - Salviati, Leonardo

AU - Trevisson, Eva

N1 - © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.

AB - COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.

KW - Journal Article

U2 - 10.1093/hmg/ddw257

DO - 10.1093/hmg/ddw257

M3 - Article

VL - 25

SP - 4256

EP - 4265

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 19

ER -