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Novel SDHD germ‐line mutations in pheochromocytoma patients
Author(s) -
Neumayer C.,
Moritz A.,
Asari R.,
Weinhäusel A.,
Hölzenbein T.,
Kretschmer G.,
Niederle B.,
Haas O. A.
Publication year - 2007
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2007.01822.x
Subject(s) - sdhd , exon , genetics , missense mutation , mutation , biology , pheochromocytoma , paraganglioma , germline mutation , medicine , gene , endocrinology , pathology
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.