A novel mutation in the SDHD gene in a family with inherited paragangliomas--implications of genetic diagnosis for follow up and treatment

Head Neck. 2003 Feb;25(2):146-51. doi: 10.1002/hed.10220.

Abstract

Background: Early detection of paragangliomas (PGs) has been linked to low morbidity after surgical resection. Recent identification of causative genes (SDHB, SDHC, and SDHD) has made it possible to detect individuals at high risk for tumors.

Methods: We identified a three-generation family, with four individuals affected with PGs. Because pedigree analysis suggested maternal imprinting (the phenotype is present only if inherited through the paternal line), the SDHD gene (PGL1) was screened.

Results: A novel mutation that causes skipping of exon 3 was identified. Ten of the seventeen tested individuals carried the mutation. All six clinically unaffected individuals inherited the mutation from their mother. Five of them are men, with a 50% risk for affected progeny.

Conclusions: To allow early treatment with low morbidity, genetic counseling is needed when familial paraganglioma is suspected. Asymptomatic carriers should be followed by cervical MRI. In addition, because pheochromocytomas may occur, catecholamine excretion can be performed. This screening should probably be proposed at 5 to 10 years of age.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Paraganglioma / diagnosis
  • Paraganglioma / genetics*
  • Pedigree
  • Pheochromocytoma / genetics
  • Sequence Analysis, RNA
  • Succinate Dehydrogenase / genetics*

Substances

  • Membrane Proteins
  • SDHD protein, human
  • Succinate Dehydrogenase