A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy

Journal of Medical Genetics
Andrea LegatiDaniele Ghezzi

Abstract

Hereditary myopathy with lactic acidosis and myopathy with deficiency of succinate dehydrogenase and aconitase are variants of a recessive disorder characterised by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, metabolic acidosis and rhabdomyolysis may occur. So far, this disease has been molecularly defined only in Swedish patients, all homozygous for a deep intronic splicing affecting mutation in ISCU encoding a scaffold protein for the assembly of iron-sulfur (Fe-S) clusters. A single Scandinavian family was identified with a different mutation, a missense change in compound heterozygosity with the common intronic mutation. The aim of the study was to identify the genetic defect in our proband. A next-generation sequencing (NGS) approach was carried out on an Italian male who presented in childhood with ptosis, severe muscle weakness and exercise intolerance. His disease was slowly progressive, with partial recovery between episodes. Patient's specimens and yeast models were investigated. Histochemical and biochemical analyses on muscle biopsy showed multiple defects affecting mitochondrial respiratory chain ...Continue Reading

References

Jan 18, 1994·Biochemistry·H A DaileyM K Johnson
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 1, 1996·Methods in Enzymology·M Sciacco, E Bonilla
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·B SchilkeE Craig
Dec 4, 2004·Biochimica Et Biophysica Acta·M BugianiM Zeviani
Jan 13, 2006·Analytical Biochemistry·Jordi TamaritJoaquim Ros
Jul 19, 2006·Molecular and Cellular Biology·Annette BiederbickRoland Lill
Apr 3, 2007·Nature Protocols·R Daniel Gietz, Robert H Schiestl
Apr 21, 2007·Methods in Cell Biology·Sabine MolikUlrich Mühlenhoff
Dec 19, 2007·Molecular and Cellular Biology·Cristy GellingUlrich Mühlenhoff
Feb 29, 2008·American Journal of Human Genetics·Fanny MochelRonald G Haller
Oct 17, 2008·Physiological Reviews·Scott K Powers, Malcolm J Jackson
Jul 2, 2009·Brain : a Journal of Neurology·Gittan KollbergElisabeth Holme
Mar 9, 2010·Biochimica Et Biophysica Acta·Petter S SanakerLaurence A Bindoff
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Alex D SheftelRoland Lill
Nov 22, 2011·Biochimica Et Biophysica Acta·Yanbo ShiTracey A Rouault
Feb 11, 2012·Molecular Biology of the Cell·Alex D SheftelRoland Lill
May 23, 2012·Biochimica Et Biophysica Acta·Roland LillUlrich Mühlenhoff
Nov 30, 2012·The Journal of Biological Chemistry·Vinay A PatilMiriam L Greenberg
Aug 3, 2013·Cold Spring Harbor Perspectives in Biology·Oliver Stehling, Roland Lill
Jan 11, 2016·Cell Metabolism·Nunziata MaioTracey A Rouault
Mar 13, 2016·Biochimica Et Biophysica Acta·Andrea LegatiMassimo Zeviani
Aug 16, 2016·The Journal of Biological Chemistry·Oleksandr GakhGrazia Isaya
Dec 3, 2016·Biochemistry. Biokhimii︠a︡·Johnny StibanLaurie S Kaguni
Dec 23, 2016·Human Molecular Genetics·Gregory P Holmes-HamptonTracey A Rouault
Jun 22, 2017·Proceedings of the National Academy of Sciences of the United States of America·Seth A CoryDavid P Barondeau

❮ Previous
Next ❯

Citations

Apr 7, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·A V Vanlander, R Van Coster
Jul 17, 2018·Brain : a Journal of Neurology·Juliana Gurgel-GiannettiFernando Kok
Sep 14, 2018·Molecular Genetics & Genomic Medicine·Denise F R RawcliffeMonica Holmberg
Apr 26, 2019·Journal of Inherited Metabolic Disease·Kyle ThompsonRobert W Taylor
Sep 8, 2018·EMBO Molecular Medicine·Aurelio ReyesMassimo Zeviani
Aug 29, 2019·American Journal of Respiratory Cell and Molecular Biology·Maki NiihoriOlga Rafikova
Jul 22, 2018·Essays in Biochemistry·Daniele Ghezzi, Massimo Zeviani
Mar 4, 2021·FEBS Letters·Mirjana Gusic, Holger Prokisch
Aug 8, 2021·Mitochondrion·Raviprasad KuthethurKapaettu Satyamoorthy
Oct 31, 2019·Biochemistry·María Georgina HerreraJavier Santos
Feb 1, 2022·IUBMB Life·Nunziata Maio, Tracey A Rouault

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
PCR
biopsy
immunoprecipitation
nuclear magnetic resonance
electrophoresis

Software Mentioned

Visual Molecular Dynamics viewer
Swiss PDB viewer
EVmutation
SIFT
FirstGlance
Jmol
Polyphen2

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.