Brauch H, Kishida T, Glavac D, Chen F, Pausch F, Höfler H, Latif F, Lerman M I, Zbar B, Neumann H P
Institute of Pathology, Technical University Munich, Germany.
Hum Genet. 1995 May;95(5):551-6. doi: 10.1007/BF00223868.
We identified a germline missense mutation at nucleotide 505 (T to C) of the VHL tumor suppressor gene in 14, apparently unrelated, VHL type 2A families from the Black Forest region of Germany. This mutation was previously identified in two VHL 2A families living in Pennsylvania (USA). All affected individuals in the 16 families shared the same VHL haplotype indicating a founder effect. This missense mutation at codon 169 (Tyr to His) would probably cause an alteration in the structure of the putative VHL protein. The association of this distinct mutation with the pheochromocytoma phenotype in VHL may help to elucidate the genetic mechanism of carcinogenesis in this multi tumor cancer syndrome.
我们在来自德国黑森林地区的14个明显无亲缘关系的2A型冯希佩尔-林道综合征（VHL）家族中，鉴定出VHL肿瘤抑制基因第505位核苷酸（从T到C）的种系错义突变。此前在美国宾夕法尼亚州的两个2A型VHL家族中也发现了这种突变。这16个家族中的所有患病个体都共享相同的VHL单倍型，表明存在奠基者效应。这个位于第169位密码子（从酪氨酸到组氨酸）的错义突变可能会导致假定的VHL蛋白结构发生改变。这种独特的突变与VHL中的嗜铬细胞瘤表型之间的关联，可能有助于阐明这种多肿瘤癌症综合征的致癌遗传机制。
