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

• 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
• ISSN: 2073-4425

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 &gt; 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.