Familial and genetic researches on three Chinese families with von Hippel-Lindau disease.
OBJECTIVE
Hemangioblastoma of the central nervous system (CNS) occur as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by germline mutation of the VHL tumor suppressor gene. 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.


METHODS
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.


RESULTS
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). Twenty VHL disease patients in the three families have the most common manifestation of CNS hemangioblastoma. The cytosine replaced the 716th guanine on four patients and three carriers of virulence gene from the first family, which made the 168th serine replaced by threonine. And no mutation was found on the 22 members of the second family. Meanwhile, it was also found that the guanine replaced the 559th cytosine on one patient and two carriers from the third family, which made the 116th leucine replaced by valine.


CONCLUSIONS
The DNA analysis of VHL germline mutations is clearly superior to clinical information to diagnose VHL disease. The CNS hemangioblastoma is the early manifestation in VHL disease. It is recommended that every patient with CNS hemangioblastoma should be screened for VHL gene mutation. The test for the VHL gene plays a key role in the discovery of asymptomatic patients and the carriers of virulence gene.
Mao
Xiao-Chun
XC
Department of Neurosurgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
Su
Zhi-Peng
ZP
Yu
Wen-Qiao
WQ
Zheng
Wei-Ming
WM
Zeng
Yan-Jun
YJ
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000208:ethnology; D001932:Brain Neoplasms / Q000209:etiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D018325:Hemangioblastoma / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000235:genetics*
D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human