A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population

Phosphoglycerate kinase (PGK)1 deficiency is an X-linked inherited disease associated with different clinical presentations, sometimes as myopathic affectation without hemolytic anemia. We present a 40-year-old male with a mild psychomotor delay and mild mental retardation, who developed progressive...

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Main Authors:	Virginia Garcia-Solaesa, Pablo Serrano-Lorenzo, Maria Antonia Ramos-Arroyo, Alberto Blázquez, Inmaculada Pagola-Lorz, Mercè Artigas-López, Joaquín Arenas, Miguel A. Martín, Ivonne Jericó-Pascual
Format:	Article
Language:	English
Published:	MDPI AG 2019-10-01
Series:	Genes
Subjects:	phosphoglycerate kinase 1 gene (<i>pgk1</i>) pgk1 deficiency myopathic form missense variant abnormalities in mrna splicing
Online Access:	https://www.mdpi.com/2073-4425/10/10/785

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spelling	doaj-892286d7436047c5a77fde46a8af07d02020-11-25T02:03:41ZengMDPI AGGenes2073-44252019-10-01101078510.3390/genes10100785genes10100785A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish PopulationVirginia Garcia-Solaesa0Pablo Serrano-Lorenzo1Maria Antonia Ramos-Arroyo2Alberto Blázquez3Inmaculada Pagola-Lorz4Mercè Artigas-López5Joaquín Arenas6Miguel A. Martín7Ivonne Jericó-Pascual8Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain, <email>ma.ramos.arroyo@navarra.es</email> (M.A.R.-A.)Laboratorio de Enfermedades Mitocondriales y Neurometabólicas. Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain, <email>pserranolorenzo.imas12@h12o.es</email> (P.S.-L.)Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain, <email>ma.ramos.arroyo@navarra.es</email> (M.A.R.-A.)Laboratorio de Enfermedades Mitocondriales y Neurometabólicas. Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain, <email>pserranolorenzo.imas12@h12o.es</email> (P.S.-L.)Department of Neurology, Complejo Hospitalario de Navarra, IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain, <email>inmaculada.pagola.lorz@navarra.es</email> (I.P.-L.)Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain, <email>ma.ramos.arroyo@navarra.es</email> (M.A.R.-A.)Laboratorio de Enfermedades Mitocondriales y Neurometabólicas. Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain, <email>pserranolorenzo.imas12@h12o.es</email> (P.S.-L.)Laboratorio de Enfermedades Mitocondriales y Neurometabólicas. Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain, <email>pserranolorenzo.imas12@h12o.es</email> (P.S.-L.)Department of Neurology, Complejo Hospitalario de Navarra, IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain, <email>inmaculada.pagola.lorz@navarra.es</email> (I.P.-L.)Phosphoglycerate kinase (PGK)1 deficiency is an X-linked inherited disease associated with different clinical presentations, sometimes as myopathic affectation without hemolytic anemia. We present a 40-year-old male with a mild psychomotor delay and mild mental retardation, who developed progressive exercise intolerance, cramps and sporadic episodes of rhabdomyolysis but no hematological features. A genetic study was carried out by a next-generation sequencing (NGS) panel of 32 genes associated with inherited metabolic myopathies. We identified a missense variant in the <i>PGK1</i> gene c.1114G > A (p.Gly372Ser) located in the last nucleotide of exon 9. cDNA studies demonstrated abnormalities in mRNA splicing because this change abolishes the exon 9 donor site. This novel variant is the first variant associated with a myopathic form of PGK1 deficiency in the Spanish population.https://www.mdpi.com/2073-4425/10/10/785phosphoglycerate kinase 1 gene (<i>pgk1</i>)pgk1 deficiencymyopathic formmissense variantabnormalities in mrna splicing
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Virginia Garcia-Solaesa Pablo Serrano-Lorenzo Maria Antonia Ramos-Arroyo Alberto Blázquez Inmaculada Pagola-Lorz Mercè Artigas-López Joaquín Arenas Miguel A. Martín Ivonne Jericó-Pascual
spellingShingle	Virginia Garcia-Solaesa Pablo Serrano-Lorenzo Maria Antonia Ramos-Arroyo Alberto Blázquez Inmaculada Pagola-Lorz Mercè Artigas-López Joaquín Arenas Miguel A. Martín Ivonne Jericó-Pascual A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population Genes phosphoglycerate kinase 1 gene (<i>pgk1</i>) pgk1 deficiency myopathic form missense variant abnormalities in mrna splicing
author_facet	Virginia Garcia-Solaesa Pablo Serrano-Lorenzo Maria Antonia Ramos-Arroyo Alberto Blázquez Inmaculada Pagola-Lorz Mercè Artigas-López Joaquín Arenas Miguel A. Martín Ivonne Jericó-Pascual
author_sort	Virginia Garcia-Solaesa
title	A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population
title_short	A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population
title_full	A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population
title_fullStr	A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population
title_full_unstemmed	A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population
title_sort	novel missense variant associated with a splicing defect in a myopathic form of pgk1 deficiency in the spanish population
publisher	MDPI AG
series	Genes
issn	2073-4425
publishDate	2019-10-01
description	Phosphoglycerate kinase (PGK)1 deficiency is an X-linked inherited disease associated with different clinical presentations, sometimes as myopathic affectation without hemolytic anemia. We present a 40-year-old male with a mild psychomotor delay and mild mental retardation, who developed progressive exercise intolerance, cramps and sporadic episodes of rhabdomyolysis but no hematological features. A genetic study was carried out by a next-generation sequencing (NGS) panel of 32 genes associated with inherited metabolic myopathies. We identified a missense variant in the <i>PGK1</i> gene c.1114G > A (p.Gly372Ser) located in the last nucleotide of exon 9. cDNA studies demonstrated abnormalities in mRNA splicing because this change abolishes the exon 9 donor site. This novel variant is the first variant associated with a myopathic form of PGK1 deficiency in the Spanish population.
topic	phosphoglycerate kinase 1 gene (<i>pgk1</i>) pgk1 deficiency myopathic form missense variant abnormalities in mrna splicing
url	https://www.mdpi.com/2073-4425/10/10/785
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A Novel Missense Variant Associated with A Splicing Defect in A Myopathic Form of PGK1 Deficiency in The Spanish Population

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