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

• Published in: Genes Vol. 10; no. 10; p. 785
• Main Authors: Garcia-Solaesa, Virginia, Serrano-Lorenzo, Pablo, Ramos-Arroyo, Maria Antonia, Blázquez, Alberto, Pagola-Lorz, Inmaculada, Artigas-López, Mercè, Arenas, Joaquín, Martín, Miguel A, Jericó-Pascual, Ivonne
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.10.2019; MDPI
• Subjects: Adenosine triphosphate; Adult; Anemia; Biopsy; Cells, Cultured; Enzymes; Genes; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - pathology; Genomes; Hemolytic anemia; Hereditary diseases; Humans; Intellectual disabilities; Intolerance; Kinases; Male; Metabolism; Metabolism, Inborn Errors - genetics; Metabolism, Inborn Errors - pathology; mRNA; Mutation; Mutation, Missense; Nervous system; Next-generation sequencing; Phosphoglycerate kinase; Phosphoglycerate Kinase - deficiency; Phosphoglycerate Kinase - genetics; Phosphoglycerate Kinase - metabolism; Phylogenetics; Proteins; Rhabdomyolysis; RNA Splicing; Spain; Spain; United Kingdom > UK; United States > US; myopathic form; abnormalities in mRNA splicing; missense variant; phosphoglycerate kinase 1 gene (PGK1); PGK1 deficiency
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes10100785

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 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.