A Hemizygous Deletion Within the PGK1 Gene in Males with PGK1 Deficiency

  • Andrea Medrano Behlmann
  • Namita A. Goyal
  • Xiaoyu Yang
  • Ping H. Chen
  • Arunkanth AnkalaEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 45)


Phosphoglycerate kinase-1 (PGK1) deficiency is a rare X-linked disorder caused by pathogenic variants in the PGK1 gene. Complete loss-of-function variants have not been reported in this gene, indicating that residual enzyme function is critical for viability in males. Therefore, copy number variants (CNVs) that include single exon or multiple exon deletions or duplications are generally not expected in individuals with PGK1 deficiency. Here we describe a 64-year-old male presenting with a family history (three additional affected males) and a personal history of childhood-onset metabolic myopathy that involves episodes of muscle pain, stiffness after activity, exercise intolerance, and myoglobinuria after exertion. Biochemical analysis on a muscle biopsy indicated significantly reduced activity (15% compared to normal) for phosphoglycerate kinase (PGK1), a glycolytic enzyme encoded by PGK1. A diagnosis of PGK1 deficiency was established by molecular analysis which detected an approximately 886 kb deletion involving the polyadenylation site in the 3′UTR of the PGK1 gene. RNA analysis showed significantly reduced PGK1 transcript levels (30% compared to normal). This is the first deletion reported in the PGK1 gene and is the first pathogenic variant involving the 3′UTR polyadenylation site of this gene. Our report emphasizes the role of 3′UTR variants in human disorders and underscores the need for exploring noncoding regions of disease-associated genes when seeking a molecular diagnosis.


3′UTR Deletion PGK1 Poly-A tail Polyadenylation Regulatory element X-linked disorder 

Supplementary material

477698_1_En_147_MOESM1_ESM.jpg (217 kb)
Fig. S1 Possible roles of position effects on PGK1 transcription. (a) Deletion of an enhancer (green square) would decrease PGK1 expression. (b) Adoption of an alternate enhancer (orange square) may modify the level of transcription and/or spatiotemporal expression. (c) Repositioning of a normally distant silencer (red triangle) would decrease PGK1 expression. (d) Deletion of an insulator (purple octagon) may lead to heterochromatin extension into the PGK1 gene, thereby decreasing expression (JPG 216 kb)


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Andrea Medrano Behlmann
    • 1
  • Namita A. Goyal
    • 2
  • Xiaoyu Yang
    • 3
  • Ping H. Chen
    • 3
  • Arunkanth Ankala
    • 1
    • 4
    Email author
  1. 1.Department of Human GeneticsEmory University School of MedicineAtlantaUSA
  2. 2.Department of NeurologyUniversity of CaliforniaIrvineUSA
  3. 3.Department of Cell BiologyEmory University School of MedicineAtlantaUSA
  4. 4.EGL Genetic Diagnostics LLCTuckerUSA

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