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.
