Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI

American Journal of Human Genetics
B BurwinkelM W Kilimann

Abstract

Deficiency of glycogen phosphorylase in the liver gives rise to glycogen-storage disease type VI (Hers disease; MIM 232700). We report the identification of the first mutations in PYGL, the gene encoding the liver isoform of glycogen phosphorylase, in three patients with Hers disease. These are two splice-site mutations and two missense mutations. A mutation of the 5' splice-site consensus of intron 14 causes the retention of intron 14 and the utilization of two illegitimate 5' splice sites, whereas a mutation of the 3' splice-site consensus of intron 4 causes the skipping of exon 5. Two missense mutations, N338S and N376K, both cause nonconservative replacements of amino acids that are absolutely conserved even in yeast and bacterial phosphorylases. We also report corrections of the PYGL coding sequence, sequence polymorphisms, and a partial PYGL gene structure with introns in the same positions as in PYGM, the gene of the muscle isoform of phosphorylase. Our findings demonstrate that PYGL mutations cause Hers disease, and they may improve laboratory diagnosis of deficiencies of the liver phosphorylase system.

References

Dec 1, 1976·The Biochemical Journal·B Lederer, W Stalmans
May 17, 1976·Clinica Chimica Acta; International Journal of Clinical Chemistry·J F KosterJ Fernandes
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C B NewgardR J Fletterick
Jan 15, 1986·Biochimica Et Biophysica Acta·E S David, M M Crerar
Aug 15, 1995·Biochimica Et Biophysica Acta·C BartramR J Beynon
Jun 1, 1995·European Journal of Pediatrics·J Fernandes
Dec 5, 1993·Journal of Molecular Biology·J W HudsonM M Crerar
Mar 20, 1998·Annals of Neurology·M VorgerdM W Kilimann

❮ Previous
Next ❯

Citations

Aug 21, 2007·Journal of Inherited Metabolic Disease·N J BeauchampM J Sharrard
Jan 16, 1999·Current Opinion in Biotechnology·J D Terwilliger, K M Weiss
Oct 19, 2007·Genes and Immunity·Y C DingS L Neuhausen
Oct 1, 2014·Molecular Genetics and Metabolism·Anne RoscherSaadet Mercimek-Mahmutoglu
Apr 7, 2016·BBA Clinical·María M Adeva-AndanyEva Ameneiros-Rodríguez
Nov 29, 2015·Pesticide Biochemistry and Physiology·Deepa GandhiSivanesan Saravanadevi
Oct 5, 2006·The Plant Journal : for Cell and Molecular Biology·David DauvilléeSteven G Ball
Jul 24, 2010·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Dong LiuHuiping Chen
Aug 21, 2010·Pediatrics International : Official Journal of the Japan Pediatric Society·Atsushi OgawaYoichi Kohno
Jan 8, 2020·Thyroid : Official Journal of the American Thyroid Association·Scott A Ochsner, Neil J McKenna
May 23, 2000·Journal of Pediatric Endocrinology & Metabolism : JPEM·O N Elpeleg
Oct 7, 2004·Endocrine Reviews·Clara BouchéAllison B Goldfine
Aug 30, 2020·Cellular Oncology (Dordrecht)·G MantiniC R Jimenez
Sep 7, 2020·Journal of Pediatric Endocrinology & Metabolism : JPEM·Shi-Qi LuKuerbanjiang Abuduxikuer
Oct 7, 2017·Indian Pediatrics·Barath Jagadisan, Prajnya Ranganath
Nov 27, 2019·European Journal of Pediatrics·Tim Rj AeppliJohannes Häberle
Jan 20, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Priya S KishnaniUNKNOWN ACMG Work Group on Diagnosis and Management of Glycogen Storage Diseases Type VI and IX
Jan 1, 2021·Microbial Pathogenesis·Lei CuiHuazhen Liu
Sep 23, 2020·The Journal of Molecular Diagnostics : JMD·Bo LiuYulan Lu
Dec 23, 2020·International Journal of Molecular Sciences·Aitana Almodóvar-PayáTomàs Pinós
May 25, 2021·Molecular Genetics and Metabolism Reports·Sarah Catharina GrünertUte Spiekerkoetter
Dec 28, 1999·Endocrinology and Metabolism Clinics of North America·J I WolfsdorfD A Weinstein
Aug 28, 2021·Genes·Sarah Catharina GrünertUte Spiekerkoetter
Apr 14, 2009·Bioorganic & Medicinal Chemistry Letters·Surendra Singh BishtRama P Tripathi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.