Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas

J Clin Endocrinol Metab. 2001 Jun;86(6):2890-4. doi: 10.1210/jcem.86.6.7547.


Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheochromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A-->G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34--36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms / genetics*
  • Amino Acid Sequence / genetics
  • Base Sequence / genetics
  • Chromosomes, Human, Pair 1 / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics*
  • Polymorphism, Genetic / genetics
  • Pseudogenes / genetics
  • Succinate Dehydrogenase
  • Syndrome
  • Transcription, Genetic


  • Membrane Proteins
  • SDHD protein, human
  • Succinate Dehydrogenase

Associated data

  • GENBANK/AB026906