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Disruption of the Responsible Gene in a Phosphoglucomutase 1 Deficiency Patient by Homozygous Chromosomal Inversion

  • Katsuyuki Yokoi
  • Yoko Nakajima
  • Tamae Ohye
  • Hidehito Inagaki
  • Yoshinao Wada
  • Tokiko Fukuda
  • Hideo Sugie
  • Isao Yuasa
  • Tetsuya Ito
  • Hiroki Kurahashi
Research Report
Part of the JIMD Reports book series (JIMD, volume 43)

Abstract

Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in the PGM1 gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in the PGM1 gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of the PGM1 gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts the PGM1 gene within intron 1. Since the initiation codon in the PGM1 gene is located within exon 1, we speculated that this inversion inactivates the PGM1 gene and was therefore responsible for the patient’s phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.

Keywords

Chromosomal inversion Congenital disorders of glycosylation Hypoglycemia PGM1 Phosphoglucomutase 1 deficiency 

Notes

Acknowledgments

We thank the patient and his family for their participation in this study. We also thank past and present members of our laboratory. This research was partly supported by the intramural research grant (29-4) for Neurological and Psychiatric Disorders of NCNP (H. Sugie).

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Copyright information

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

Authors and Affiliations

  • Katsuyuki Yokoi
    • 1
    • 2
  • Yoko Nakajima
    • 1
  • Tamae Ohye
    • 2
  • Hidehito Inagaki
    • 2
  • Yoshinao Wada
    • 3
  • Tokiko Fukuda
    • 4
  • Hideo Sugie
    • 5
  • Isao Yuasa
    • 6
  • Tetsuya Ito
    • 1
  • Hiroki Kurahashi
    • 2
    • 7
    • 8
  1. 1.Department of PediatricsFujita Health University School of MedicineToyoakeJapan
  2. 2.Division of Molecular Genetics, Institute for Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan
  3. 3.Department of Obstetric MedicineOsaka Women’s and Children’s HospitalOsakaJapan
  4. 4.Department of PediatricsHamamatsu University School of MedicineHamamatsuJapan
  5. 5.Faculty of Health and Medical SciencesTokoha UniversityHamamatsuJapan
  6. 6.Division of Legal MedicineTottori University Faculty of MedicineYonagoJapan
  7. 7.Genome and Transcriptome Analysis CenterFujita Health UniversityToyoakeJapan
  8. 8.Center for Collaboration in Research and EducationFujita Health UniversityToyoakeJapan

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