Search

Mutations in genes coding for three of the four components of mitochondrial complex II can cause paragangliomas (PGLs)/pheochromocytomas. The three genes include SDHB, -C, and -D. SDHC and SDHD anchor the catalytic subunits SDHA and -B of mitochondrial complex II in the inner mitochondrial membrane. SDHD is maternally imprinted but SDHB and -C are not. While SDHD and -- to a lesser degree -- SDHB mutations have been found in many cases of hereditary PGL, SDHC mutations are rare. This article reviews the SDHC mutations described to date and discusses possible mechanisms of tumorigenesis.

Mutations in SDHC cause autosomal dominant paraganglioma, type 3 (PGL3), and have to date been demonstrated in only one family. Here, we report on a novel mutation in a patient with a malignant, catecholamine-producing paraganglioma at the carotid bifurcation. The mutation is a G--T transversion at position +1 of intron 5 of the SDHC gene, leading to the deletion of exon 5 and a shift in the reading frame.

Nonchromaffin paragangliomas (PGLs) are usually benign, neural-crest-derived, slow-growing tumours of parasympathetic ganglia. Between 10% and 50% of cases are familial and are transmitted as autosomal dominant traits with incomplete and age-dependent penetrance.