A FAMILY WITH HEREDITARY EXTRAADRENAL PARAGANGLIOMAS WITHOUT EVIDENCEFOR MUTATIONS IN THE VON-HIPPEL-LINDAU-DISEASE OR RET GENES

OBJECTIVES To characterize a family with hereditary paraganglioma, and to search for germline mutations in the von Hippel-Lindau disease (VH L) tumour suppressor gene and the ret proto-oncogene. DESIGN Patient r ecords and histopathological reports were reviewed. Available tumour s amples were reinvestigated using immunohistochemical techniques. The V HL gene was investigated by single strand conformational polymorphism analysis of PCR products amplified from exons 1, 2 and 3 and the 3' un translated region. The ret gene was analysed by amplifying and sequenc ing exons 10, 11 and 16.PATIENTS A family with paragangliomas in three consecutive generations was investigated. RESULTS The affected indivi duals were found to have multiple extra-adrenal paragangliomas. All th ree affected individuals had retroperitoneal tumours, and two also had paraganglioma in the neck. No mutations of the VHL or ret genes were detected. CONCLUSIONS The described family may represent a novel domin antly inherited neuroendocrine tumour syndrome.