Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family

A. Patócs, Peter Gergics, Katalin Balogh, Miklos Toth, Ferenc Fazakas, Istvan Liko, K. Rácz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

Original languageEnglish
Article number29
JournalBMC Medical Genetics
Volume9
DOIs
Publication statusPublished - Apr 16 2008

Fingerprint

von Hippel-Lindau Disease
Mutation
Genes
Pheochromocytoma
Codon
Epididymis
Genetic Counseling
Genetic Association Studies
Human Chromosomes
Tumor Suppressor Genes
Renal Cell Carcinoma
Pancreas
Spinal Cord
Phenotype
Kidney
Brain

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family. / Patócs, A.; Gergics, Peter; Balogh, Katalin; Toth, Miklos; Fazakas, Ferenc; Liko, Istvan; Rácz, K.

In: BMC Medical Genetics, Vol. 9, 29, 16.04.2008.

Research output: Contribution to journalArticle

Patócs, A. ; Gergics, Peter ; Balogh, Katalin ; Toth, Miklos ; Fazakas, Ferenc ; Liko, Istvan ; Rácz, K. / Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family. In: BMC Medical Genetics. 2008 ; Vol. 9.
@article{b83b134770fa4b8589a7b246b957eef1,
title = "Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family",
abstract = "Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.",
author = "A. Pat{\'o}cs and Peter Gergics and Katalin Balogh and Miklos Toth and Ferenc Fazakas and Istvan Liko and K. R{\'a}cz",
year = "2008",
month = "4",
day = "16",
doi = "10.1186/1471-2350-9-29",
language = "English",
volume = "9",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family

AU - Patócs, A.

AU - Gergics, Peter

AU - Balogh, Katalin

AU - Toth, Miklos

AU - Fazakas, Ferenc

AU - Liko, Istvan

AU - Rácz, K.

PY - 2008/4/16

Y1 - 2008/4/16

N2 - Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

AB - Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

UR - http://www.scopus.com/inward/record.url?scp=43049095689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43049095689&partnerID=8YFLogxK

U2 - 10.1186/1471-2350-9-29

DO - 10.1186/1471-2350-9-29

M3 - Article

C2 - 18416845

AN - SCOPUS:43049095689

VL - 9

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

M1 - 29

ER -