The N131S Mutation in the von Hippel-Lindau Gene in a Japanese Family with Pheochromocytoma and Hemangioblastomas

• IMANAKA Mari

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• IIDA Keiji

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• TAKAHASHI Kentaro

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• TSUJI Kazuo

  Division of Endocrinology and Metabolism, Nishi-Kobe Medical Center

• NISHIZAWA Hitoshi

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• FUKUOKA Hidenori

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• TAKENO Ryoko

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• TAKAHASHI Yutaka

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

• OKIMURA Yasuhiko

  Department of Basic Allied Medicine, Kobe University School of Medicine

• KAJI Hidesuke

  Division of Physiology/Metabolism, University of Hyogo

• CHIHARA Kazuo

  Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

抄録

Von Hippel-Lindau (VHL) disease (VHLD) is a hereditary autosomal dominant syndrome that causes various benign and malignant tumors. VHLD is caused by mutations in the VHL tumor suppressor gene. Here, we report a mutation in the VHL gene in a Japanese family with VHLD type 2A, characterized by pheochromocytoma (PHE), and hemangioblastomas (HAB) in both the retina and thoracic spinal cord but without renal cell carcinoma (RCC). We identified a heterozygous A to G point mutation at the second base of codon 131 of the VHL protein (pVHL). This mutation was predicted to convert codon 131 from asparagine to serine (N131S). Although most mutations in VHLD type 2A have been detected in the α domain of pVHL, the present mutated amino acid was located at the region encoding the β domain of pVHL. Previous patients with the N131K or N131T mutation in pVHL developed VHLD type 2B with RCC or VHLD type 1 without PHE, respectively. We also identified somatic loss of heterozygosity (LOH) at chromosome 3p25-26 in the adrenal tumor of the patient. The results of our study suggest that not only the location of mutation but also the altered amino acid may be critical for determining the clinical phenotype of VHLD. LOH was associated with the development of PHE in a patient with the N131S mutation in pVHL.<br>

収録刊行物

• Endocrine Journal

  Endocrine Journal 53 (6), 819-827, 2006

  一般社団法人 日本内分泌学会

キーワード

• von Hippel-Lindau disease
• Pheochromocytoma
• Hemangioblastoma
• DNA diagnosis
• Renal cell carcinoma
• Loss of heterozygosity

詳細情報

• CRID: 1390001206300555392
• NII論文ID: 10020612693
• NII論文ID: 130004443274
• NII書誌ID: AA10901436
• DOI: 10.1507/endocrj.k06-046
• ISSN: 13484540
• ISSN: 09188959
• Web Site: http://www.jstage.jst.go.jp/article/endocrj/53/6/53_6_819/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007191539
• 本文言語コード: en
• データソース種別:
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  • CiNii Articles
  • KAKEN
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