AI Article Synopsis

  • Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors often linked to specific gene mutations, with this study focusing on a case of sporadic OZ-PGL in a 32-year-old female experiencing severe hypertension during pregnancy.
  • The patient was diagnosed with a noradrenaline-secreting OZ-PGL after surgery, revealing a missense mutation in the hypoxia-inducible factor 2α (HIF2α) gene, which likely contributed to tumor development without being inherited from parents.
  • This case is unique as it connects a specific somatic HIF2α mutation to OZ-PGL, suggesting that patients without known germline mutations should still undergo testing

Article Abstract

Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70% of cases, occur in association with succinate dehydrogenase complex iron sulfur subunit B () or gene mutations. The aim of the current study was to determine whether a somatic genetic defect in the hypoxia-inducible factor 2α (α) gene was present in a case of sporadic OZ-PGL. A 32-year-old African female presented with uncontrolled hypertension during the first trimester of pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery, precipitating a hypertensive crisis. Thereafter, the patient was diagnosed with noradrenaline-secreting OZ-PGL. A complete blood count identified mild normocytic anemia of an inflammatory origin. Surgical removal of the tumor resulted in normalization of plasma and urinary normetanephrine levels. Genetic testing for germline mutations (including large deletions) in the von Hippel-Lindau tumor suppressor, , and genes was normal. However, a heterozygous missense mutation (c.1589Cys>Tyr) was detected in exon 12 of α, which results in a substitution of alanine 530 with valine (Ala530Val) in the HIF2α protein. A germline mutation was excluded based on the negative results of blood DNA testing. A three-dimensional homology model of Ala530Val was constructed, which showed impaired HIF2α/VHL interaction and decreased HIF2α ubiquitination. H-high-resolution magic-angle-spinning nuclear magnetic resonance spectroscopy detected low succinate levels and high α and β glucose levels. To the best of our knowledge, the present case represents the first of its kind to associate a somatic α gain-of-function mutation with OZ-PGL. It is therefore recommended that patients without germline mutations should be tested for α mutations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403169PMC
http://dx.doi.org/10.3892/ol.2017.5599DOI Listing

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