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Table 1 Genotype-phenotype correlation for VHL disease and possible responsible pathofysiological mechanisms.

From: A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL) syndrome type 2C

Type VHL

Type of VHL gene germline mutation

Retinal HAB

CNS HAB

RCC

PHEO

Mechanisms for VHL mediated tumorigenesis

1

Missense

+

+

+

-

Loss of function (i.e. HIF decreased)

 

Microdeletions

     
 

Insertions

     
 

Splice site

     
 

Nonsense

     
 

Large deletions

     

2A

Missense

+

+

-

+

Loss of function (HAB) (i.e. HIF decreased)

      

Gain of function (PHEO) Fibronectin binding decreased

2B

Missense

+

+

+

+

Loss of function (HAB + RCC) (i.e. HIF decreased)

      

Gain of function (PHEO) Fibronectin binding decreased

2C

Missense

-

-

-

+

Gain of function (PHEO) Fibronectin binding decreased

  1. VHL: Von Hippel-Lindau, HAB: haemangioblastoma, CNS: central nervous system, RCC: renal cell carcinoma, PHEO: pheochromocytoma, HIF: hypoxia-inducible factor; +: tumour present, -: no tumour