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

Endocrine Journal

Hidesuke KAJI²  Hitoshi NISHIZAWA⁴  Kentaro TAKAHASHI⁴  Kazuo TSUJI¹  Ryoko TAKENO⁴  Mari IMANAKA⁴  Yasuhiko OKIMURA³  Hidenori FUKUOKA⁴  Keiji IIDA⁴  Yutaka TAKAHASHI⁴  Kazuo CHIHARA⁴ 

[1] Division of Endocrinology and Metabolism, Nishi-Kobe Medical Center;Division of Physiology/Metabolism, University of Hyogo;Department of Basic Allied Medicine, Kobe University School of Medicine;Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine

关键词: von Hippel-Lindau disease;    Pheochromocytoma;    Hemangioblastoma;    DNA diagnosis;    Renal cell carcinoma;    Loss of heterozygosity;   

DOI  :  10.1507/endocrj.K06-046

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(26)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.

【 授权许可】

Unknown