Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation

Human Mutation
C KubischT J Jentsch

Abstract

McArdle disease is a rare autosomal recessive disorder of the muscle glycogen metabolism caused by mutations in the muscle glycogen phosphorylase gene. Until now, a total number of 11 different mutations in the coding region or splice sites of the myophosphorylase gene have been identified. In contrast to a wealth of data on the RNA and protein level, little information is available on the genomic sequence of the corresponding gene. To facilitate molecular diagnosis of McArdle disease, we reinvestigated the genomic structure of the myophosphorylase gene and sequenced about 9.8 kilobases (kb) on the genomic level. By choosing 14 intronic primer pairs, we were able to amplify the complete human coding sequence as well as the adjacent splice sites of the 20 exons. Direct sequencing of the amplification products of a consanguineous Turkish family with typical McArdle disease revealed a novel single base pair deletion in exon 18, which predicts a frameshift and a premature termination of the protein. In summary, we established a system for molecular diagnosis of McArdle disease based on a revised genomic structure of the myophosphorylase gene and demonstrated its feasibility by identification of a novel mutation.

References

Feb 1, 1992·Trends in Biochemical Sciences·M F Browner, R J Fletterick
Jan 1, 1991·Proteins·G D SchulerD J Lipman
Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
Jan 1, 1995·Muscle & Nerve. Supplement·S DiMauroL P Rowland
Jan 1, 1995·Muscle & Nerve. Supplement·S TsujinoS DiMauro
Mar 15, 1994·American Journal of Medical Genetics·A E PulverG Nestadt
Oct 1, 1993·Nature Genetics·M Grompe
Jul 22, 1993·The New England Journal of Medicine·S TsujinoS DiMauro
Aug 1, 1996·Neurology·M el-SchahawiS DiMauro
Apr 1, 1996·Journal of the Neurological Sciences·A MartinuzziC Angelini
Jul 1, 1997·Neuromuscular Disorders : NMD·P TanN G Laing
Nov 1, 1959·The Journal of Clinical Investigation·R SCHMID, R MAHLER
Jun 1, 1959·Proceedings of the National Academy of Sciences of the United States of America·W F MommaertsK Seraydarian

❮ Previous
Next ❯

Citations

Jan 1, 2003·Muscle & Nerve·Marcus DeschauerStephan Zierz
Jan 16, 2007·Current Neurology and Neuroscience Reports·G Nogales-GadeaA L Andreu
Jan 26, 2002·Journal of the Neurological Sciences·Georgios M HadjigeorgiouSalvatore DiMauro
Aug 18, 1999·Journal of the Neurological Sciences·C BrunoS DiMauro
Feb 5, 2000·Neurologic Clinics·G D Vladutiu
Mar 29, 2000·Pediatric Neurology·B T Darras, N R Friedman
Oct 26, 2002·Neuromuscular Disorders : NMD·Georgios M HadjigeorgiouSalvatore DiMauro
Apr 7, 2011·Zoological Science·Gyu-Hwi NamHeui-Soo Kim
Jun 11, 2011·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·F MiteffD O Hutchinson
Jul 1, 2010·Journal of Biomedicine & Biotechnology·Anibh M DasSabine Illsinger
Aug 12, 2009·Muscle & Nerve·Aleksandra A Nadaj-PaklezaTanya Stojkovic
Jun 3, 2015·Muscle & Nerve·Petros PetrouTheodoros Kyriakides
Jun 28, 2005·Molecular Genetics and Metabolism·Paul J IsacksonGeorgirene D Vladutiu
Mar 6, 2015·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J-Y HogrelP Laforêt
Apr 29, 2015·Human Mutation·Gisela Nogales-GadeaTomàs Pinós
Dec 26, 2001·Molecular Genetics and Metabolism·M DeschauerS Zierz
Dec 19, 2017·Medicine and Science in Sports and Exercise·Irene Rodríguez-GómezIgnacio Ara
Apr 1, 2003·Annals of Neurology·Andrea MartinuzziStefano Bertelli
Aug 21, 2003·Muscle & Nerve·Josep GámezJoaquín Arenas
Nov 13, 2014·The Cochrane Database of Systematic Reviews·Rosaline QuinlivanBenedikt Schoser
Sep 14, 2019·Neurology. Genetics·Anna RubegniDenise Cassandrini
Dec 16, 1998·Current Opinion in Neurology·S DiMauro, C Bruno
May 12, 2018·Acta Neurologica Scandinavica·J-B NouryF Rannou
Nov 12, 2018·Acta neurologica Belgica·Paulo José LorenzoniRosana Herminia Scola
Sep 18, 2021·Journal of Inherited Metabolic Disease·Chiara PizzamiglioRosaline Quinlivan

❮ Previous
Next ❯

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.