Hereditary paragangliomas caused by mutations in the SDHD gene

Introduction. Identification of the gene involved with hereditary paragangliomas (PGL1) was the objective. At least 50% of all glomus tumours have a positive family history via an autosomal dominant inheritance with genomic imprinting linked to chromosome 11q 23. Methods. DNA sequences revealed the presence of the SDHD gene in the PGL1 gene-related glomus families. Results. In almost all PGL-1-related glomus families, four germline mutations were found in the SDHD gene (Succinate dehydrogenase, subunit D). This is a special (tumour-suppressor) gene, encoding a mitochondrial protein that takes part in the respiratory chain complex. Surprisingly, the SDHD mutation was found in 40% of non-familial cases. Conclusion. The discovery of the SDHD gene encoding for hereditary paragangliomas offers both clinical and scientific possibilities of presymptomatic DNA research for optimal genetic counselling, efficient clinical examination, radiodiagnostics and follow-up, insight into the mechanism of genomic imprinting and into the molecular process from mutation to tumour in extremely slow-growing paragangliomas.