title: In Silico Analysis Identification of a Novel Germ-Line VHL Mutation in a Patient of Malignant Pheochromocytoma.
abstract: OBJECTIVE
  Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor syndrome caused by a VHL gene mutation. Here we report a novel mutation of VHL in a patient diagnosed with malignant pheochromocytoma at the age of 17.
  
  
  METHODS
  A 17-year-old female was referred for paroxysmal supraventricular tachycardia and anemia. She was diagnosed with a left adrenal pheochromocytoma based on biochemical and imaging studies. A left adrenalectomy was performed. Six months after surgery, metastatic lesions were suspected in the lung. The histopathologic findings of thoracoscopic lung biopsy specimens confirmed metastasis of the malignant pheochromocytoma.
  
  
  RESULTS
  Genetic analysis of VHL showed a novel missense mutation at codon 194 (V194G) in exon 3. This mutation was inherited from the paternal allele, and a loss of heterozygosity was noted in 3 of the patient's distinct tumors. Two independent in silico analyses suggested that this amino acid substitution was pathogenic.
  
  
  CONCLUSIONS
  We identified a novel missense mutation of VHL in a young patient with malignant pheochromocytoma.
authors: Clinical Research Institute, National Hospital Organization Kyoto Medical Center Department of Diabetes, Endocrinology and Metabolism, Tango Central Hospital.
authors: Sachiko-Tsukamoto
authors: ST
authors: Kawashima
authors: Clinical Research Institute, National Hospital Organization Kyoto Medical Center.
authors: Takeshi
authors: T
authors: Usui
authors: Department of Endocrinology and Metabolism, Yokohama City Seibu Hospital, St. Marianna University School of Medicine.
authors: Ayumi
authors: A
authors: Tenjin
authors: Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine.
authors: Shiko
authors: S
authors: Asai
authors: Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine.
authors: Yasushi
authors: Y
authors: Tanaka
authors: Department of Pathology, St. Marianna University School of Medicine, Japan.
authors: Masahiro
authors: M
authors: Hoshikawa
authors: Clinical Research Institute, National Hospital Organization Kyoto Medical Center.
authors: Akira
authors: A
authors: Shimatsu
authors: Department of Endocrinology and Metabolism, Yokohama City Seibu Hospital, St. Marianna University School of Medicine.
authors: Takuyuki
authors: T
authors: Katabami