Germ‐line Mutation Analysis in Patients with von Hippel‐Lindau Disease in Japan: An Extended Study of 77 Families

Yoshida, Minoru; Ashida, Shingo; Kondo, Keiichi; Kobayashi, Kazuki; Kanno, Hiroshi; Shinohara, Nobuo; Shitara, Nobuyuki; Kishida, Takeshi; Kawakami, Satoshi; M, Baba; Yamamoto, Isao; Hosaka, Masahiko; Shuin, Taro; Yao, Masahiro

doi:10.1111/j.1349-7006.2000.tb00933.x

Cited by 47 publications

(54 citation statements)

References 25 publications

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“…Dinucleotide CpG hotspot mutations were found in both Japanese and Caucasian patients; however, the incidence was lower in Japanese patients [Yoshida et al, 2000]. Missense mutations occurred at a lower incidence overall in Japanese patients [Clinical Research Group for VHL in Japan, 1995;Shuin et al, 1995] and in VHL Type 1 Japanese families when compared to Western families [Fukino et al, 2000;Yoshida et al, 2000]. These variations could be attributed to possible environmental or ethnic factors.…”

Section: Ethnic Diversitymentioning

confidence: 95%

“…Initially it was noted that phenotypes in Caucasian VHL families paralleled Japanese families for most mutations . Later studies by Yoshida et al [2000] found that mutations p.Arg113Ter, p.Gln132Ter, p.Leu158Val, and p.Cys162Tyr, which were previously associated with VHL Type 1 in Western cultures [Crossey et al, 1994a;Glavac et al, 1996;Maher et al, 1996;Zbar et al, 1996], were associated with VHL Type 2 in Japanese families [Clinical Research Group for VHL in Japan, 1995;Yoshida et al, 2000]. A study of 15 Korean patients showed the majority of VHL Type 1 mutations were nonmissense mutations, similar to those found in Japan and Western cultures [Cho et al, 2009].…”

Section: Ethnic Diversitymentioning

confidence: 99%

“…Methylation of the VHL promoter is a common mechanism of inactivation (8-11%) in sporadic RCC [Herman et al, 1994;Nickerson et al, 2008;Smits et al, 2008]. Dinucleotide CpG hotspot mutations were found in both Japanese and Caucasian patients; however, the incidence was lower in Japanese patients [Yoshida et al, 2000]. Missense mutations occurred at a lower incidence overall in Japanese patients [Clinical Research Group for VHL in Japan, 1995;Shuin et al, 1995] and in VHL Type 1 Japanese families when compared to Western families [Fukino et al, 2000;Yoshida et al, 2000].…”

Section: Ethnic Diversitymentioning

confidence: 99%

“…Families with this mutation often have low penetrance and a mild phenotype; some families have multiple asymptomatic carriers Hes et al, 2000;Kishida et al, 1995;Weirich et al, 2002;Yoshida et al, 2000]. Genetic polymorphism was shown to be unlikely after screening multiple non-VHL patients [Hes et al, 2000;Weirich et al, 2002].…”

Section: Pathogenic Variantsmentioning

confidence: 99%

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Genetic analysis of von Hippel-Lindau disease

et al. 2010

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Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

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Section: Ethnic Diversitymentioning

confidence: 95%

Section: Ethnic Diversitymentioning

confidence: 99%

Section: Ethnic Diversitymentioning

confidence: 99%

Section: Pathogenic Variantsmentioning

confidence: 99%

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Genetic analysis of von Hippel-Lindau disease

et al. 2010

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“…Although the mutation per se was not novel [8], we identified a loss of heterozygosity (LOH) in the affected adrenal gland of one of the patients in this family. This family case study may be helpful to understand the mechanism by which both HAB and PHE develop in VHLD.…”

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confidence: 97%

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

et al. 2006

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Abstract. 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.

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Somatic von Hippel–Lindau disease gene mutation in clear‐cell renal carcinomas associated with end‐stage renal disease/acquired cystic disease of the kidney

Yoshida

Yao

Ishikawa

et al. 2002

Genes Chromosomes & Cancer

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It has been documented that renal cell carcinomas (RCCs) occur frequently in patients treated with long-term dialysis, especially in cases of end-stage renal disease (ESRD)/acquired cystic disease of the kidney (ACDK). To address the molecular pathogenesis of ESRD/ACDK-associated RCCs, we examined 14 RCCs (7 clear-cell and 7 papillary carcinomas) in patients receiving dialysis for somatic mutations of the von Hippel-Lindau disease (VHL) gene as well as of the tyrosine kinase domain of the MET oncogene. Direct sequencing analyses revealed that three tumors exhibited VHL frameshifts (618delA, 386-395del10-bp, and 723-724insTC). One of the VHL mutated tumors showed additional loss of heterozygosity at the VHL gene locus. Histopathologic and clinical data demonstrated that the three tumors having VHL mutations were clear-cell RCCs occurring in ESRD with 55, 106, and 156 months of dialysis history, respectively. We did not find any tumors with mutations in the tyrosine kinase domain of the MET. These results demonstrated that the VHL tumor-suppressor gene is also involved in a subset of clear-cell RCCs occurring in ESRD/ACDK, as in the case of sporadic clear-cell RCCs. However, mutations of the MET oncogene could not be found in the seven ESRD/ACDK-associated papillary RCCs examined.

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Germ‐line Mutation Analysis in Patients with von Hippel‐Lindau Disease in Japan: An Extended Study of 77 Families

Cited by 47 publications

References 25 publications

Genetic analysis of von Hippel-Lindau disease

Genetic analysis of von Hippel-Lindau disease

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

Somatic von Hippel–Lindau disease gene mutation in clear‐cell renal carcinomas associated with end‐stage renal disease/acquired cystic disease of the kidney

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