Multifocal Paraganglioma and Pheochromocytoma Due to Truncated SDHD Mutation

Urology. 2018 Jun:116:63-67. doi: 10.1016/j.urology.2018.01.012. Epub 2018 Mar 12.

Abstract

Objective: Pheochromocytoma and paraganglioma (PPGL) are rare autosomal dominant disorders derived from the neural crest chromaffin tissues of the autonomic nervous system. The succinate dehydrogenase complex subunit D (SDHD) gene has been implicated as one of the pathogenic genes. Although more than 100 SDHD mutations have been reported, the phenotype-genotype association remains unclear.

Methods: We reported a case of a patient who presented with multifocal PPGLs and with a rare SDHD mutation, and reviewed the phenotype-genotype association of SDHD.

Results: We identified a pathogenic variant of SDHD (c.170-1G>T, NM_003002.3), which caused the complete deletion of exon 3 in the transcript and resulted in a shorter and unstable SDHD mRNA. And truncated SDHD mutations were prone to cause multifocal PPGL, whereas missense SDHD mutations usually caused unifocal lesions.

Conclusion: This is the first report linking the c.170-1G>T variant to multifocal tumors. We recommend whole-body imaging examinations and close, regular follow-up for these patients, given the risk of multifocal tumor development.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Carotid Body Tumor / genetics
  • Codon, Nonsense
  • DNA, Neoplasm / genetics
  • Ear Neoplasms / genetics*
  • Ear, Inner
  • Exons / genetics
  • Female
  • Gene Deletion
  • Genetic Association Studies
  • Humans
  • Models, Molecular
  • Neoplasms, Multiple Primary / genetics*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics*
  • Point Mutation*
  • Protein Conformation
  • RNA, Messenger / genetics
  • Sequence Analysis, DNA
  • Succinate Dehydrogenase / chemistry
  • Succinate Dehydrogenase / genetics*
  • Whole Body Imaging

Substances

  • Codon, Nonsense
  • DNA, Neoplasm
  • RNA, Messenger
  • SDHD protein, human
  • Succinate Dehydrogenase