Case report: We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual.
A 9-year-and-5-month old male patient was diagnosed with polyglobulia after an accident at 8 years of age. Proband's mother reported that the patient displayed fatigue and peripheral cyanosis during exercise. The physical exam showed a tumor in the right testicle. This was confirmed to be a cyst in the right epididymis was identified by a testicular ultrasound. Due to family history of VHL disease (4 generations, 12 patients with VHLd), genetic testing was performed on the mother, where an exon 3 deletion in the VHL gene was identified. The mother died due to complications of a CNS hemangioblastoma at 30Y. A peripheral blood sample was then obtained from the patient, where the same exon 3 deletion was identified by MLPA. Complete VHL gene sequencing was then performed on the proband's sample which identified a new S139C(c.416C>G) missense mutation, revealing that the patient was a compound heterozygote. This missense mutation was not previously reported. There was also no information on the proband's father; thus it is not confirmed whether the missense mutation was paternally inherited or de novo. Prediction tools such as PolyPhen2, Mutationassesor, Provean, and SIFT suggests it is deleterious. Due to the clinical presentation and molecular biology studies, the patient was diagnosed with both familial erythrocytosis type 2 and VHL disease.