TITLE

A Nonsense Mutation in the Acid α-Glucosidase Gene Causes Pompe Disease in Finnish and Swedish Lapphunds

AUTHOR(S)
Seppälä, Eija H.; Reuser, Arnold J. J.; Lohi, Hannes
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.
ACCESSION #
87624963

 

Related Articles

  • Identification of eight novel mutations of the acid α-glucosidase gene causing the infantile or juvenile form of glycogen storage disease type II. Wan, L.; Lee, C.-C.; Hsu, C.-M.; Hwu, W.-L.; Yang, C.-C.; Tsai, C.-H.; Tsai, F.-J. // Journal of Neurology;Jun2008, Vol. 255 Issue 6, p831 

    Glycogen-storage disease type II (GSDII; OMIM #232300), an autosomal recessive disorder caused by a deficiency of the glycogen hydrolysis enzyme acid α-glucosidase (acid GAA; acid maltase, EC. 3.2.10.20), results in the accumulation of glycogen in the lysosome. We performed a molecular...

  • Autophagy and Mistargeting of Therapeutic Enzyme in Skeletal Muscle in Pompe Disease. Fukuda, Tokiko; Ahearn, Meghan; Roberts, Ashley; Mattaliano, Robert J.; Zaal, Kristien; Ralston, Evelyn; Plotz, Paul H.; Raben, Nina // Molecular Therapy;Dec2006, Vol. 14 Issue 6, p831 

    Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid α-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of...

  • Structural and biochemical studies on Pompe disease and a “pseudodeficiency of acid α-glucosidase”. Tajima, Youichi; Matsuzawa, Fumiko; Aikawa, Sei-ichi; Okumiya, Toshika; Yoshimizu, Michiru; Tsukimura, Takahiro; Ikekita, Masahiko; Tsujino, Seiichi; Tsuji, Akihiko; Edmunds, Tim; Sakuraba, Hitoshi // Journal of Human Genetics;Nov2007, Vol. 52 Issue 11, p898 

    We constructed structural models of the catalytic domain and the surrounding region of human wild-type acid α-glucosidase and the enzyme with amino acid substitutions by means of homology modeling, and examined whether the amino acid replacements caused structural and biochemical changes in...

  • Structural modeling of mutant α-glucosidases resulting in a processing/transport defect in Pompe disease. Sugawara, Kanako; Saito, Seiji; Sekijima, Masakazu; Ohno, Kazuki; Tajima, Youichi; Kroos, Marian A.; Reuser, Arnold J. J.; Sakuraba, Hitoshi // Journal of Human Genetics;Jun2009, Vol. 54 Issue 6, p324 

    To elucidate the mechanism underlying transport and processing defects from the viewpoint of enzyme folding, we constructed three-dimensional models of human acid α-glucosidase encompassing 27 relevant amino acid substitutions by means of homology modeling. Then, we determined in each...

  • Bioinformatic and biochemical studies point to AAGR-1 as the ortholog of human acid α-glucosidase in Caenorhabditis elegans. Sikora, Jakub; Uřinovská, Jana; Majer, Filip; Poupětová, Helena; Hlavatá, Jitka; Kostrouchová, Marta; Ledvinová, Jana; Hřebíček, Martin // Molecular & Cellular Biochemistry;Aug2010, Vol. 341 Issue 1/2, p51 

    Human acid α-glucosidase (GAA, EC 3.2.1.20) is a lysosomal enzyme that belongs to the glycoside hydrolase family 31 (GH31) and catalyses the hydrolysis of α-1,4- and α-1,6-glucosidic linkages at acid pH. Hereditary deficiency of GAA results in lysosomal glycogen storage disease type II...

  • Screening of Late-Onset Pompe Disease in a Sample of Mexican Patients With Myopathies of Unknown Etiology: Identification of a Novel Mutation in the Acid α-Glucosidase Gene. Alcántara-Ortigoza, Miguel Angel; González-del Angel, Ariadna; Barrientos-Rios, Rehotbevely; Cupples, Courtney; Garrido-García, Luis Martín; De León-Bojorge, Beatríz; Alva-Chaire, Adriana del Carmen // Journal of Child Neurology;Aug2010, Vol. 25 Issue 8, p1034 

    Pompe disease or glycogen-storage disease type 2 (GSD2, OMIM 232300) is an autosomal recessive disorder caused by mutations in the acid α-glucosidase gene. Late-onset GSD2 resembles some limb-girdle and Becker muscular dystrophies. The screening of GSD2 through the measurement of acid...

  • A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease). Aryani, Omid; Manshadi, Masoumeh; Tondar, Mahdi; Khalili, Elham; Kamalidehghan, Behnam; Ahmadipour, Fatemeh; Fani, Somayeh; Houshmand, Massoud // Molecular Biology Reports;Sep2014, Vol. 41 Issue 9, p6211 

    Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme ( GAA; EC.3.2.1.3) leading to intracellular aggregations of glycogenin muscles. The infantile-onset type is the most life-threatening form of this...

  • Immune Responses and Hypercoagulation in ERT for Pompe Disease Are Mutation and rhGAA Dose Dependent. Nayak, Sushrusha; Doerfler, Phillip A.; Porvasnik, Stacy L.; Cloutier, Denise D.; Khanna, Richie; Valenzano, Ken J.; Herzog, Roland W.; Byrne, Barry J. // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    Enzyme replacement therapy (ERT) with recombinant human acid-α-glucosidase (rhGAA) is the only FDA approved therapy for Pompe disease. Without ERT, severely affected individuals (early onset) succumb to the disease within 2 years of life. A spectrum of disease severity and progression exists...

  • Prenatal diagnosis of Pompe disease - Enzyme assay or molecular testing? Prajnya, R.; Rehder, C.; Phadke, Shubha; Bali, D. // Indian Pediatrics;Nov2011, Vol. 48 Issue 11, p901 

    We report two cases which illustrate that enzyme assay results alone, may at times be equivocal and inconclusive in the prenatal diagnosis of storage disorders like Pompe disease and therefore, if the proband's mutation is known, targeted mutation analysis of fetal DNA is the most reliable...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics