missense mutation at codon 194 (V194G) in exon 3
A 17-year-old female was referred for paroxysmal supraventricular tachycardia and anemia. SHe had a 2-year history of episodic sweating and palpitations. She was diagnosed with a left adrenal pheochromocytoma. A left adrenalectomy was performed. One month after the left adrenalectomy, CT and 131I-MIBG scintigraphy showed a mass in the para-aortic region located superior to the left adrenal gland; later, histology confirmed this to be an extraadrenal pheochromocytoma. A second laparoscopic surgery was performed to remove a para-aortic mass. Six months after surgery, metastatic lesions were suspected in the lung, enlarged iliac lymph nodes, bilateral iliac masses, and a lumbar spinal mass. The histopathologic findings of thoracoscopic lung biopsy specimens confirmed metastasis of the malignant pheochromocytoma. Genetic testing confirmed a novel missense mutation at codon 194 (V194G) in exon 3 of the VHL gene, which 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.