K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma.
OBJECTIVE
Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of familial paragangliomas and phaeochromocytomas. Twenty-three SDHB mutations have been identified to date.


METHODS
We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E) identified in an Australian family. The proband was diagnosed with phaeochromocytoma at an early age following an unexpected hypertensive crisis and was found to be SDHB mutation-positive. Subsequent genetic screening of 26 family members has identified 17 mutation-positive relatives. In addition to the proband, four mutation positive relatives were found to have clinical symptoms or a lesion and/or catecholamine excess after the identification of the mutation led to further evaluation. Both the proband and an uncle have required surgical removal of a tumour.


CONCLUSIONS
This family indicates the importance of germline screening of first-degree relatives when a patient presents with an apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a patient with a nonsecretory paraganglioma is found.
McDonnell
Ciara M
CM
Centre for Hormone Research, Department of Endocrinology & Diabetes, Royal Children's Hospital, Parkville, Victoria, Australia.
Benn
Diana E
DE
Marsh
Deborah J
DJ
Robinson
Bruce G
BG
Zacharin
Margaret R
MR
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000601:surgery; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins; D008297:Male; D020125:Mutation, Missense; D010235:Paraganglioma / Q000235:genetics* / Q000601:surgery; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics* / Q000601:surgery; D021122:Protein Subunits / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase