Large deletion causing von Hippel-Lindau disease and hereditary breast cancer syndrome.

[von hippel-lindau disease]

Patients with intragenic mutations of the VHL gene have a typical disease presentation . However in cases of large VHL gene deletions which involve other genes in the proximity of the VHL gene a presentation of the disease can be different . To investigate whether large VHL deletions that remove the FANCD 2 gene have an effect on the disease phenotype , we studied a family with a 50 Â kb large deletion encompassing these two genes . Four patients in this family were affected by VHL -related lesions . However one carrier of the deletion also had bilateral ductal breast cancer at age 46 and 49 . Both tumors were of ~2 Â cm in diameter . On one side lymph nodes were affected . One tumor was ER- and PR-negative (HER 2 s unknown ) and the second was ER- and PR-positive , and HER 2 -negative . Our study suggests that a deletion of FANCD 2 gene , an important gene in the DNA repair pathway , may be associated with an increased risk of breast cancer , but further studies are needed in this regard .