Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants
| Autor: | Allan M. Lund, Mario Ćuk, Willy Lissens, Marianne Hoogeveen-Westerveld, Ans T. van der Ploeg, Vidosava Rakocevic Stojanovic, Dicky J. J. Halley, Robert J. Pomponio, Piraye Serdaroglu, Shingo Kumamoto, Wim Robberecht, Marian A. Kroos, Hossein Najmabadi, Stojan Peric, Eugen Mengel, Simon Jones, Margreet G. E. M. Ausems, A. Farouk, Jose E. Barcena Llona, Anna Tylki-Szymańska, Kristof Verhoeven, Marc D'Hooghe, Suely Kazue Nagahashi Marie, Barbara Plecko, Helen Michelakakis, Andreas Herzog, Luisa Bonafé, E. Garcia-Delgado, A. Tarnutzer, Mohammad Shboul, E. Munteis Olivas, Aynur Küçükçongar, Mohammad-Hassan Karimi-Nejad, Mojca Zerjav Tansek, J. Hurst, Maria Venâncio, Toshika Okumiya, Eduard Paschke, Persephone Augoustides-Savvopoulou, Irene Mavridou, Ksenija Fumić, Juan Bautista Lorite, Nadine A. M. E. van der Beek, Arnold J. J. Reuser, E. Maravi, Baziel G.M. van Engelen, Danielle Majoor-Krakauer |
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| Přispěvatelé: | Clinical Genetics, Pediatrics, University of Zurich, Reuser, Arnold |
| Rok vydání: | 2012 |
| Předmět: |
2716 Genetics (clinical)
Mutagenesis (molecular biology technique) 610 Medicine & health Biology medicine.disease_cause computer.software_genre Frameshift mutation 03 medical and health sciences 0302 clinical medicine 1311 Genetics Databases Genetic Genetics medicine Missense mutation Humans Genetic Predisposition to Disease Gene Genetics (clinical) 030304 developmental biology 0303 health sciences Mutation Database Glycogen Storage Disease Type II Point mutation Intron alpha-Glucosidases GAA Pompe disease α-glucosidase acid maltase glycogenosis lysosomal storage disease Stop codon 3. Good health 10036 Medical Clinic computer 030217 neurology & neurosurgery |
| Zdroj: | Human Mutation, 33(8), 1161-1165. Wiley-Liss Inc. |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.22108 |
| Popis: | Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid a-glucosidase (EC; 3.2.1.20/3) can be caused by numerous pathogenic variants in the GAA gene. The Pompe Disease Mutation Database at aims to list all variants and their effect. This update reports on 94 variants. We examined 35 novel and 34 known mutations by site-directed mutagenesis and transient expression in COS-7 cells or HEK293T cells. Each of these mutations was given a severity rating using a previously published system, based on the level of acid a-glucosidase activity in medium and transfected cells and on the quantity and quality of the different molecular mass species in the posttranslational modification and transport of acid a-glucosidase. This approach enabled to classify 55 missense mutations as pathogenic and 13 as likely nonpathogenic. Based on their nature and the use of in silico analysis (Alamut (R) software), 12 of the additional 25 novel mutations were predicted to be pathogenic including 4 splicing mutations, 6 mutations leading to frameshift, and 2 point mutations causing stop codons. Seven of the additional mutations were considered nonpathogenic (4 silent and 3 occurring in intron regions), and 6 are still under investigation. Hum Mutat 33:11611165, 2012. (c) 2012 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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