title: VHL2C phenotype in a German von Hippel-Lindau family with concurrent VHL germline mutations P81S and L188V.
abstract: Von Hippel-Lindau disease (VHL) is a multitumor syndrome that develops on the basis of germline mutations in the VHL tumor suppressor gene. Genotype-phenotype correlations have helped to stratify the disease into VHL type 1 (without pheochromocytoma) and VHL type 2A, 2B, and 2C (with pheochromocytoma). VHL2C is characterized by a pheochromocytoma-only phenotype. We report on the P81S germline mutation in a German VHL2C family with the previously identified L188V mutation. The concurrent P81S mutation was identified by novel screening approaches including denaturing HPLC and sequencing. We show the co-segregation of these two mutations with the disease and discuss their possible impact on pVHL function and phenotype.
authors.affiliation: Institute of Pathology, Technische Universität München, D-81675 Munich, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Weirich
authors.forename: Bettina
authors.initials: B
authors.lastname: Klein
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wöhl
authors.forename: Dieter
authors.initials: D
authors.lastname: Engelhardt
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D005858:Germany; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human