A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.

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...

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Autores principales:	Eija H Seppälä, Arnold J J Reuser, Hannes Lohi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c4ece5f35ca47fb8c285f0d495bf440
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spelling	oai:doaj.org-article:6c4ece5f35ca47fb8c285f0d495bf4402021-11-18T07:57:24ZA nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.1932-620310.1371/journal.pone.0056825https://doaj.org/article/6c4ece5f35ca47fb8c285f0d495bf4402013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23457621/?tool=EBIhttps://doaj.org/toc/1932-6203Pompe 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.Eija H SeppäläArnold J J ReuserHannes LohiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56825 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eija H Seppälä Arnold J J Reuser Hannes Lohi A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
description	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.
format	article
author	Eija H Seppälä Arnold J J Reuser Hannes Lohi
author_facet	Eija H Seppälä Arnold J J Reuser Hannes Lohi
author_sort	Eija H Seppälä
title	A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
title_short	A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
title_full	A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
title_fullStr	A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
title_full_unstemmed	A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.
title_sort	nonsense mutation in the acid α-glucosidase gene causes pompe disease in finnish and swedish lapphunds.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6c4ece5f35ca47fb8c285f0d495bf440
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A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds.

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