Hereditary paraganglioma in South Africa : An investigation of the Succinate-ubiquinone Oxidoreductase subunit genes, SDHB, SDHC and SDHD

Abstract

Paraganglioma (PGL) are tumours occurring in the head-and-neck -, intra-abdominal - and thoracic paraganglia. Germ-line mutations in genes encoding the subunits of mitochondrial succinate dehydrogenase complex II (SDHB, SDHC, SDHD) and the SDHAF2 gene are involved in hereditary paraganglioma. Our aim was to identify mutations within these genes in ten South African PGL families. Individuals were screened for mutations in SDHAF2 using Sanger sequencing and Multiplex Ligationdependent Probe Amplification was utilised to investigate large rearrangements in these genes. A 7905bp SDHB exon 3 deletion [c.201-4429_287-933del], was identified in all SA families. The same deletion is reported as a founder mutation in Dutch PGL families. Genotype analysis revealed a common haplotype at the SDHB locus between SA and Dutch patients, indicating common ancestry. This is the first Afrikaner SDHB founder mutation. These results now enable predictive testing of other family members and allow better clinical management of the families.