Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma

Eur J Hum Genet. 2002 Aug;10(8):457-61. doi: 10.1038/sj.ejhg.5200829.

Abstract

Familial paraganglioma is a dominantly inherited disorder characterised by the development of highly vascular tumours in the head and neck. Recently, a relationship between hereditary tumours derived from the autonomic nervous system and germline mutations in the gene encoding succinate dehydrogenase complex subunit D (SDHD) is increasingly a subject of study. Familial paraganglioma syndrome is embryologically related to phaeochromocytoma, another neuroendocrine tumour that shows great aetiological and genetic heterogeneity. Some hereditary phaeochromocytomas may be associated with germline mutations in VHL, RET and NF1 genes in genetic disorders such as von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2) and neurofibromatosis type 1 (NF 1), respectively. However, there are many cases that cannot be explained by mutations in these genes. In this report, we describe two previously unreported mutations in two patients from 25 unrelated kindreds with phaeochromocytoma and/or paraganglioma disorders and with or without familial antecedents: a mutation featuring the change of tryptophan to a termination codon in exon 2, and a 4-bp deletion in exon 4 that results in a truncated protein. We also describe one missense substitution of uncertain significance. The patients had previously tested negative for germline mutations in VHL and RET genes and had not been previously selected. The involvement of SDHD mutations in familial phaeochromocytoma and/or paraganglioma predisposition is of considerable interest since other studies have shown these alterations to be associated with highly expressed angiogenic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / enzymology
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Age of Onset
  • Aged
  • Base Sequence
  • Child
  • DNA Primers
  • Electron Transport Complex II
  • Family
  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Mutation*
  • Oxidoreductases / genetics*
  • Paraganglioma / complications
  • Paraganglioma / genetics*
  • Pheochromocytoma / complications
  • Pheochromocytoma / enzymology
  • Pheochromocytoma / genetics*
  • Polymerase Chain Reaction
  • Succinate Dehydrogenase / genetics*

Substances

  • DNA Primers
  • Multienzyme Complexes
  • Oxidoreductases
  • Electron Transport Complex II
  • Succinate Dehydrogenase