Author(s):
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Hes, F.J.; Luijt, R.B. van der; Janssen, A.L.; Zewald, R.A.; Jong, G.J. de;
Lenders, J.W.M.
; Links, T.P.; Luyten, G.P.M.; Sijmons, R.H.; Eussen, H.J.; Halley, D.J.; Lips, C.J.M.; Pearson, P.L.; Ouweland, A.M.W. van den; Majoor-Krakauer, D.F.
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Subject:
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IGMD 5: Health aging / healthy living NCEBP 14: Cardiovascular diseases UMCN 2.2: Vascular medicine and diabetes |
Abstract:
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The current clinical diagnosis of Von Hippel-Lindau (VHL) disease demands at least one specific a sporadic VHL manifestation in a patient with familial VHL disease, or, in asporadic patient, at least two or more hemangioblastomas or a single hemangioblastoma in combination with a typical visceral lesion. To evaluate this definition, we studied the frequency of germline VHL mutation in three patients groups: (i) multi-organ involvement (classic VHL), (ii) limited VHL manifestations meeting criteria (non-classic VHL) and (iii) patients with VHL-associated tumors not meeting current diagnostic VHL criteria. In addition, we validated multiplex ligation-dependent probe amplification (MLPA) as a rapid and reliable quantitative method for the identification of germline VHL deletions. The frequency of germline VHL mutations was very high in classic VHL cases with multi-organ involvement (95%), lower in non-classic cases that meet current diagnostic criteria but have limited VHL manifestations or single-organ involvement (24%) and low (3.3%), but tangible in cases not meeting current diagnostic VHL criteria. The detection of germline VHL mutations in patients or families with limited VHL manifestations, or single-organ involvement is relevant for follow-up of probands and early identification of at-risk relatives.
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