» Articles » PMID: 17024664

Genotype-phenotype Correlations in Von Hippel-Lindau Disease

Overview
Journal Hum Mutat
Specialty Genetics
Date 2006 Oct 7
PMID 17024664
Citations 93
Authors
Affiliations
Soon will be listed here.
Abstract

von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome resulting from mutations in the VHL tumor suppressor gene. VHL disease displays marked variation in expression and the presence of pheochromocytoma has been linked to missense VHL mutations. We analyzed genotype-phenotype correlations in 573 individuals with VHL disease. Routine clinical and radiological surveillance of VHL patients and at-risk relatives was associated with increased detection of retinal angiomatosis (73 vs. 59% of cases) and a reduction in age at diagnosis of renal cell carcinoma (RCC) (44.0+/-10.9 vs. 39.7+/-10.3 years). We confirmed the association of pheochromocytoma with missense mutations described previously, but stratifying missense mutations into those that resulted in substitution of a surface amino acid and those that disrupted structural integrity demonstrated that surface amino acid substitutions conferred a higher pheochromocytoma risk. Age at first manifestation of VHL disease was significantly earlier (P=0.001), and age-related risks of retinal angiomas and RCC were higher (P=0.022 and P=0.0008, respectively) in individuals with a nonsense or frameshift mutation than in those with deletions or missense mutations that disrupted the structural integrity of the VHL gene product (pVHL). These results extend genotype-phenotype-protein structure correlations in VHL disease and provide a baseline for future chemoprevention studies in VHL disease.

Citing Articles

Early Screening and Identification of an Asymptomatic Pheochromocytoma in a Child with Von Hippel-Lindau: A Case Report.

Schmeling K, Schuh J, Lal D, Becktell K Case Rep Oncol. 2024; 17(1):1309-1315.

PMID: 39545024 PMC: 11563656. DOI: 10.1159/000541527.


Genotype-phenotype correlation of ocular von Hippel-Lindau disease in Koreans.

Hwang S, Kang S, Kim J, Kim S PLoS One. 2024; 19(10):e0311665.

PMID: 39374255 PMC: 11458008. DOI: 10.1371/journal.pone.0311665.


Familial and early recurrent pheochromocytoma in a child with a novel in-frame duplication variant of .

Suzuki Y, Iemura R, Sutani A, Mizuno Y, Adachi E, Ushiama M Clin Pediatr Endocrinol. 2024; 33(4):229-237.

PMID: 39359666 PMC: 11442702. DOI: 10.1297/cpe.2024-0020.


Genetics, Pathophysiology, and Current Challenges in Von Hippel-Lindau Disease Therapeutics.

Gomez-Virgilio L, Velazquez-Paniagua M, Cuazozon-Ferrer L, Silva-Lucero M, Gutierrez-Malacara A, Padilla-Mendoza J Diagnostics (Basel). 2024; 14(17).

PMID: 39272694 PMC: 11393980. DOI: 10.3390/diagnostics14171909.


The genetic differences between types 1 and 2 in von Hippel-Lindau syndrome: comprehensive meta-analysis.

Azimi F, Naseripour M, Aghajani A, Kasraei H, Chaibakhsh S BMC Ophthalmol. 2024; 24(1):343.

PMID: 39138406 PMC: 11323439. DOI: 10.1186/s12886-024-03597-1.