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Novel Association of Early Onset Hepatocellular Carcinoma with Transaldolase Deficiency

  • Charles A. LeDuc
  • Elizabeth E. Crouch
  • Ashley Wilson
  • Jay Lefkowitch
  • Mirjam M. C. Wamelink
  • Cornelis Jakobs
  • Gajja S. Salomons
  • Xiaoyun Sun
  • Yufeng Shen
  • Wendy K. ChungEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 12)

Abstract

We evaluated a family with a 16-month-old boy with cirrhosis and hepatocellular carcinoma and his 30-month-old brother with cirrhosis. After failing to identify a diagnosis after routine metabolic evaluation, we utilized a combination of RNA-Seq and whole exome sequencing to identify a novel homozygous p.Ser171Phe Transaldolase (TALDO1) variant in the proband, his brother with cirrhosis, as well as a clinically asymptomatic older 8-year-old brother. Metabolite analysis and enzymatic testing of TALDO1 demonstrated elevated ribitol, sedoheptitol, and sedoheptulose-7P, and lack of activity of TALDO1 in the three children homozygous for the p.Ser171Phe mutation. Our findings expand the phenotype of transaldolase deficiency to include early onset hepatocellular carcinoma in humans and demonstrate that, even within the same family, individuals with the same homozygous mutation demonstrate a wide range of phenotypes.

Keywords

Hepatocellular Carcinoma Exome Sequencing Glycogen Storage Disease Urine Organic Acid Normal Platelet Count 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Birthe Roos and Erwin Jansen are kindly acknowledged for their analytical contributions.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Charles A. LeDuc
    • 1
  • Elizabeth E. Crouch
    • 2
  • Ashley Wilson
    • 1
  • Jay Lefkowitch
    • 3
  • Mirjam M. C. Wamelink
    • 4
  • Cornelis Jakobs
    • 4
  • Gajja S. Salomons
    • 4
  • Xiaoyun Sun
    • 5
  • Yufeng Shen
    • 5
    • 6
    • 7
  • Wendy K. Chung
    • 1
    • 8
    • 9
    Email author
  1. 1.Department of PediatricsColumbia UniversityNew YorkUSA
  2. 2.Department of NeuroscienceColumbia UniversityNew YorkUSA
  3. 3.Department of PathologyColumbia UniversityNew YorkUSA
  4. 4.Metabolic Unit, Department of Clinical ChemistryVU University Medical Center AmsterdamAmsterdamThe Netherlands
  5. 5.JP Sulzberger Columbia Genome CenterColumbia UniversityNew YorkUSA
  6. 6.Initiative in Systems BiologyColumbia UniversityNew YorkUSA
  7. 7.Department of Biomedical InformaticsColumbia UniversityNew YorkUSA
  8. 8.Department of MedicineColumbia UniversityNew YorkUSA
  9. 9.New YorkUSA

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