In Silico Analysis Identification of a Novel Germ-Line VHL Mutation in a Patient of Malignant Pheochromocytoma.

OBJECTIVE

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor syndrome caused by a VHL gene mutation. Here we report a novel mutation of VHL in a patient diagnosed with malignant pheochromocytoma at the age of 17.

METHODS

A 17-year-old female was referred for paroxysmal supraventricular tachycardia and anemia. She was diagnosed with a left adrenal pheochromocytoma based on biochemical and imaging studies. A left adrenalectomy was performed. Six months after surgery, metastatic lesions were suspected in the lung. The histopathologic findings of thoracoscopic lung biopsy specimens confirmed metastasis of the malignant pheochromocytoma.

RESULTS

Genetic analysis of VHL showed a novel missense mutation at codon 194 (V194G) in exon 3. This mutation was inherited from the paternal allele, and a loss of heterozygosity was noted in 3 of the patient's distinct tumors. Two independent in silico analyses suggested that this amino acid substitution was pathogenic.

CONCLUSION

We identified a novel missense mutation of VHL in a young patient with malignant pheochromocytoma.