Section of Endocrine Surgery, Division of General Surgery, Medical University, Vienna, Austria (C. Neumayer, R. Asari, B. Niederle); Children's Cancer Research Institute, Vienna, Austria (A. Moritz, O. A. Haas); Austrian Research Centers, Seibersdorf, Austria (A. Weinhäusel); Division of Vascular Surgery, Medical University, Vienna, Austria (T. Hölzenbein, G. Kretschmer).
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Novel SDHD germ-line mutations in pheochromocytoma patients
Article first published online: 15 JUN 2007
DOI: 10.1111/j.1365-2362.2007.01822.x
Additional Information
How to Cite
Neumayer, C., Moritz, A., Asari, R., Weinhäusel, A., Hölzenbein, T., Kretschmer, G., Niederle, B. and Haas, O. A. (2007), Novel SDHD germ-line mutations in pheochromocytoma patients. European Journal of Clinical Investigation, 37: 544–551. doi: 10.1111/j.1365-2362.2007.01822.x
C. Neumayer and A. Moritz contributed equally to this study; B. Niederle and O. A. Haas share senior authorship. This work was conceived and conducted within the framework of the ‘EU COST B19 action’.
Publication History
- Issue published online: 15 JUN 2007
- Article first published online: 15 JUN 2007
- Received 9 July 2006; accepted 20 March 2007
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Keywords:
- Germ-line mutations;
- pheochromocytoma;
- SDHD.
Abstract
Background SDHD germ-line mutations predispose to pheochromocytoma (PCC) and paraganglioma (PGL).
Material and methods The incidence and types of SDHD germ-line mutations are determined in 70 patients with apparently sporadic adrenal and extra-adrenal PCC.
Results SDHD sequence variants were identified in the germ line of five patients. Two of three novel mutations were in exon 1 and one in exon 3. One patient had a codon 1 missense mutation (M1K) and a concurrent 3-bp deletion in intron 1. Three of 10 family members had only the exon 1 mutation, whereas one had only the intron 1 mutation. The other exon 1 mutation resulted from a deletion of nucleotides 28–33 with a 12-bp in-frame insertion (c.28_33 del ins TAGGAGGCCCTA). This mutation generated a premature stop codon after codon 9 and was also present in the brother who had a bilateral PCC. The third patient with a carotid body tumour, with an abdominal and a thoracic PGL had a 12-bp deletion in exon 3 (codons 91–94, c.271_282 del). Her father carried the same mutation and had bilateral carotid body tumours. Two further patients, one with six PGL, carried a previously described H50R polymorphism, whose disease-specific relevance is currently unclear. The three patients with bona fide SDHD mutations were younger than those without germ-line mutations.
Conclusion SDHD germ-line mutations are rare in patients with PCC, but their identification is an important prerequisite for the clinical care and appropriate management of affected individuals and their families.