This study shows the clinical characteristics of three large Chinese families with VHL disease and evaluates the consequence of the genetic test for the diagnosis of VHL disease and clinical screening of the family members. DNA is extracted from peripheral blood in 43 members from three large families with VHL disease and amplified by PCR to three exons of the VHL gene. The PCR products were directly sequenced and the mutations compared with the Human Gene Mutation Database. The ages of the patients who are given the initial diagnosis ranged from 16 to 47 years (mean: 31 years), and the mean time was 17.3 months (2-30 months) from the emergence of the symptom to patients' first visit. Furthermore, the gender distribution was 20% female (4) and 80% male (16). Von Hippel-Lindau disease is seen in 12 members of a Chinese family. Molecular diagnosis is confirmed in only 7 family members. The proband (male; deceased) has retinal capillary hemangioma; hemangioblastoma, 2 of his brothers (deceased) have pancreatic cancer, a third brother has renal cancer and hemangioblastoma, and 5 nephews have hemangioblastoma. There are three members who are asymptomatic carriers, but are young and may be before the age of onset. The mutation p.S168T (c.503G>C) was referred to in the paper by c.716G>C due to a difference in transcript sequence. At least 5 additional members had VHL phenotypes, but had all passed away before genetic testing. It could be assumed their genetic mutation due to pedigree showing future linear relations of this mutation all in generation III. ACMG evidence codes: 'PP1' based on segregation results, 'PP2' because they observe a missense variant in gene where missense variants are common mechanism of disease, 'PP4' because the patients phenotypes and family history are highly specific for a disease with single genetic etiology.

This study shows the clinical characteristics of three large Chinese families with VHL disease and evaluates the consequence of the genetic test for the diagnosis of VHL disease and clinical screening of the family members. DNA is extracted from peripheral blood in 43 members from three large families with VHL disease and amplified by PCR to three exons of the VHL gene. The PCR products were directly sequenced and the mutations compared with the Human Gene Mutation Database. The ages of the patients who are given the initial diagnosis ranged from 16 to 47 years (mean: 31 years), and the mean time was 17.3 months (2-30 months) from the emergence of the symptom to patients' first visit. Furthermore, the gender distribution was 20% female (4) and 80% male (16). Von Hippel-Lindau disease is seen in 12 members of a Chinese family. Molecular diagnosis is confirmed in only 7 family members. The proband (male; deceased) has retinal capillary hemangioma; hemangioblastoma, 2 of his brothers (deceased) have pancreatic cancer, a third brother has renal cancer and hemangioblastoma, and 5 nephews have hemangioblastoma. There are three members who are asymptomatic carriers, but are young and may be before the age of onset. The mutation p.S168T (c.503G>C) was referred to in the paper by c.716G>C due to a difference in transcript sequence. At least 5 additional members had VHL phenotypes, but had all passed away before genetic testing. It could be assumed their genetic mutation due to pedigree showing future linear relations of this mutation all in generation III. ACMG evidence codes: 'PP1' based on segregation results, 'PP2' because they observe a missense variant in gene where missense variants are common mechanism of disease, 'PP4' because the patients phenotypes and family history are highly specific for a disease with single genetic etiology.