Clinical and mutation analysis of four Chinese families with von Hippel-Lindau disease

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von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposed to the development of tumors in a variety of body organs. The major etiopathogenesis of VHL is a mutation of the VHL tumor-suppressor gene on the short arm of chromosome 3 (3p25-26). We report on the clinical and molecular features of four Chinese kindreds with VHL disease. The VHL gene was screened for mutation using a direct DNA sequencing analysis and a multiplex ligation-dependent probe amplification (MLPA) for 44 volunteers from these four families. Any unaffected person, with germline VHL gene mutation, was required to undergo further examination, surveillance and treatment. The main lesions and the average diagnostic year of the 20 patients were central nervous system hemangioblastoma (60 %, 34.92 years), renal lesion (60 %, 39.08 years), pancreatic lesion (60 %, 37.67 years), adrenal pheochromocytoma (25 %, 37.8 years) and retinal hemangioblastoma (10 %, 25.5 years). Direct sequencing detected nucleotide substitutions or small deletions in three families and MLPA revealed exon 1 deletion in family A. The five asymptomatic patients were initially diagnosed by genetic analysis and verified radiologically or surgically. The spectrum of clinical manifestation of VHL in the mainland Chinese population is similar to the observation in Western kindreds. Genetic testing, which plays a crucial role in early diagnosis asymptomatic patients, is obviously superior to clinical informations when diagnosing VHL disease. The members of VHL disease family may benefit from pedigree study, genetic testing, periodic follow-up, early diagnosis and prompt treatment.