Novel SDHD germ‐line mutations in pheochromocytoma patients

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.