Improved Detection of Germline Mutations in Korean VHL Patients by Multiple Ligation-dependent Probe Amplification Analysis

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome characterized by the development of tumors in the eye, brain, spinal cord, inner ear, adrenal gland, pancreas, kidney, and epididymis, associated with germline mutations in the VHL gene. We used sequentially sequencing method and multiple ligation-dependent probe amplification (MLPA) analysis and detected germline mutations in the VHL in 15/15 (100%) of VHL patients fulfilling the clinical criteria. Of the 15 distinct mutations detected, large deletions were detected in 5/15 (33.3%) patients, including 4/15 (26.7%) partial deletions and 1/15 (6.6%) deletion of the entire VHL gene by MLPA and the remainder were point mutations detected by sequencing method, of which five mutations were novel. Using MLPA analysis, we detected large deletions including both partial deletions and complete gene deletion, which has not been reported in Korean VHL patients. In conclusion, sequential application of sequencing method and MLPA analysis might make possible to identify germline mutations in most patients with VHL

A case of carotid body paraganglioma and haemangioblastoma of the spinal cord in a patient with the N131K missense mutation in the VHL gene

The article describes paraganglioma case in woman with von Hippel–Lindau disease. She was found to be a carrier of a rare germline mutation in the VHL gene (393C>A; N131K). The patient developed large, untypical for von Hippel–Lindau disease, carotid body paraganglioma at the common carotid artery bifurcation. The carotid body paraganglioma coexisted with the haemangioblastoma situated intramedullary in region C5/C6. The haemangioblastoma reached the right-sided dorsal part of the spinal cord in section C5/C6. It produced radicular symptoms within C5/C6, followed by the later paresis of the right limbs. The haemangioblastoma was resected completely. Twelve months after the operation, the spinal symptoms receded and the carotid body paraganglioma still was asymptomatic. The current case of carotid body paraganglioma in patient with the 393C>A (N131K) missense mutation in the VHL gene, supports association of this specific mutation and VHL disease type 2, and suggests its correlation with susceptibility to paragangliomas

Beyond the Evidence of the New Hypertension Guidelines. Blood pressure measurement – is it good enough for accurate diagnosis of hypertension? Time might be in, for a paradigm shift (I)

Despite widespread availability of a large body of evidence in the area of hypertension, the translation of that evidence into viable recommendations aimed at improving the quality of health care is very difficult, sometimes to the point of questionable acceptability and overall credibility of the guidelines advocating those recommendations. The scientific community world-wide and especially professionals interested in the topic of hypertension are witnessing currently an unprecedented debate over the issue of appropriateness of using different drugs/drug classes for the treatment of hypertension. An endless supply of recent and less recent "drug-news", some in support of, others against the current guidelines, justifying the use of selected types of drug treatment or criticising other, are coming out in the scientific literature on an almost weekly basis. The latest of such debate (at the time of writing this paper) pertains the safety profile of ARBs vs ACE inhibitors. To great extent, the factual situation has been fuelled by the new hypertension guidelines (different for USA, Europe, New Zeeland and UK) through, apparently small inconsistencies and conflicting messages, that might have generated substantial and perpetuating confusion among both prescribing physicians and their patients, regardless of their country of origin. The overwhelming message conveyed by most guidelines and opinion leaders is the widespread use of diuretics as first-line agents in all patients with blood pressure above a certain cut-off level and the increasingly aggressive approach towards diagnosis and treatment of hypertension. This, apparently well-justified, logical and easily comprehensible message is unfortunately miss-obeyed by most physicians, on both parts of the Atlantic. Amazingly, the message assumes a universal simplicity of both diagnosis and treatment of hypertension, while ignoring several hypertension-specific variables, commonly known to have high level of complexity, such as: - accuracy of recorded blood pressure and the great inter-observer variability, - diversity in the competency and training of diagnosing physician, - individual patient/disease profile with highly subjective preferences, - difficulty in reaching consensus among opinion leaders, - pharmaceutical industry's influence, and, nonetheless, - the large variability in the efficacy and safety of the antihypertensive drugs. The present 2-series article attempts to identify and review possible causes that might have, at least in part, generated the current healthcare anachronism (I); to highlight the current trend to account for the uncertainties related to the fixed blood pressure cut-off point and the possible solutions to improve accuracy of diagnosis and treatment of hypertension (II)

Von hippel-lindaus disease: Report of three cases and review of the literature

The authors present the autopsy findings of two related patients and the biopsy findings of a thrid member of the family. The oldest member was 34 years old at death and on postmortem examination he had haemangioblastomas in the retina, cerebellum, medulla and spinal cord. Other findings were renal cell carcinoma, phaechromocytoma, cysts of kidney and pancreas, hydromyelia and atypical meningiomas. His brother died when 30 years old. The autopsy revealed haemangioblastomas of cerebellum, renal cell carcinoma and a clear cell cystadenoma of epididymus. The third patient was the daughter of the first and presented with headache and dizziness. CT-scan showed a cerebellar haemangioblastoma. Epidemiological considerations on the commonest visceral and CNS lesions and a review of current diagnostic criteria are discussed.Os autores relatam os achados de autópsia de dois pacientes de uma mesma família e o diagnóstico por biópsia de hemangioblastoma de um terceiro membro desta mesma família. O primeiro paciente tinha 34 anos por ocasião do óbito e os achados de necrópsia mostraram hemangioblastoma de retina, cerebelo, bulbo e medula espinhal, além de carcinoma renal, feocromocitoma, lesões císticas de rim e pâncreas, hidromielia e meningiomas atípicos. Seu irmão morreu com 30 anos de idade e a autópsia revelou hemangioblastomas de cerebelo, carcinoma renal e cistoadenoma de células claras de epididimo. A terceira paciente era filha do primeiro paciente e apresentou cefaléia e ataxia. A tomografia computadorizada mostrou lesão cerebelar cística e a biópsia confirmou tratar-se de hemangioblastoma. São feitas considerações epidemiológicas sobre lesões viscerais e do sistema nervoso mais comumente encontradas, além de discutir critérios diagnósticos