Abstract:
Familial paraganglioma is a dominantly inherited disorder characterised by the development of highly
vascular tumours in the head and neck. Recently, a relationship between hereditary tumours derived
from the autonomic nervous system and germline mutations in the gene encoding succinate dehydro genase complex subunit D (SDHD) is increasingly a subject of study. Familial paraganglioma syndrome is
embryologically related to phaeochromocytoma, another neuroendocrine tumour that shows great
aetiological and genetic heterogeneity. Some hereditary phaeochromocytomas may be associated with
germline mutations in VHL, RET and NF1 genes in genetic disorders such as von Hippel ¿ Lindau disease
(VHL), multiple endocrine neoplasia type 2 (MEN 2) and neurofibromatosis type 1 (NF 1), respectively.
However, there are many cases that cannot be explained by mutations in these genes. In this report, we
describe two previously unreported mutations in two patients from 25 unrelated kindreds with phaeo chromocytoma and/or paraganglioma disorders and with or without familial antecedents: a mutation
featuring the change of tryptophan to a termination codon in exon 2, and a 4-bp deletion in exon 4 that
results in a truncated protein. We also describe one missense substitution of uncertain significance. The
patients had previously tested negative for germline mutations in VHL and RET genes and had not been
previously selected. The involvement of SDHD mutations in familial phaeochromocytoma and/or para ganglioma predisposition is of considerable interest since other studies have shown these alterations to
be associated with highly expressed angiogenic factors.
