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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-09-0399v1 161/3/495    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gergics, P. Articles by Racz, K. PubMed PubMed Citation Articles by Gergics, P. Articles by Racz, K.

Germline VHL gene mutations in Hungarian families with von Hippel–Lindau disease and patients with apparently sporadic unilateral pheochromocytomas

2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 46 Szentkirályi Street, Budapest H-1088, Hungary¹ Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, 9 Roosevelt Square, Budapest H-1051, Hungary² Gedeon Richter Ltd, 19 Gyomroi Street, Budapest H-1103, Hungary³ Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Street, Debrecen H-4012, Hungary⁴ Regional University Centre of Excellence in Environmental Industry Based on Natural Resource, Szent Istvan University, 1 Pater Karoly Street, Godollo H-2103, Hungary

(Correspondence should be addressed to K Racz; Email: racz{at}bel2.sote.hu)

Objective: Von Hippel–Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations or deletions of the VHL tumor-suppressor gene. Germline VHL gene alterations may be also present in patients with apparently sporadic pheochromocytoma (ASP), although a wide variation in mutation frequencies has been reported in different patient cohorts.

Design: Herein, we report the analysis of the VHL gene in Hungarian families with VHL disease and in those with ASP.

Methods: Seven families (35 members) with VHL disease and 37 unrelated patients with unilateral ASP were analyzed. Patients were clinically evaluated and the VHL gene was analyzed using direct sequencing, multiplex ligation-dependent probe amplification, and real-time PCR with SYBR Green chemistry.

Results: Disease-causing genetic abnormalities were identified in each of the seven VHL families and in 3 out of the 37 patients with ASP (one nonsense and six missense mutations, two large gene deletions and one novel 2 bp deletion). Large gene deletions and other genetic alterations resulting in truncated VHL protein were found only in families with VHL type 1, whereas missense mutations were associated mainly, although not exclusively, with VHL type 2B and type 2C.

Conclusions: The spectrum of VHL gene abnormalities in the Hungarian population is similar to that observed in Western, Japanese, or Chinese VHL kindreds. The presence of VHL gene mutations in 3 out of the 37 patients with ASP suggests that genetic testing is useful not only in patients with VHL disease but also in those with ASP.