Stolle C, Glenn G, Zbar B, Humphrey J S, Choyke P, Walther M, Pack S, Hurley K, Andrey C, Klausner R, Linehan W M
Genetic Diagnostic Laboratory, University of Pennsylvania, Philadelphia, USA.
Hum Mutat. 1998;12(6):417-23. doi: 10.1002/(SICI)1098-1004(1998)12:6<417::AID-HUMU8>3.0.CO;2-K.
von Hippel-Lindau disease (VHL) is an inherited neoplastic disorder characterized by the development of tumors in the eyes, brain, spinal cord, inner ear, adrenal gland, pancreas, kidney, and epididymis. The VHL tumor suppressor gene was identified in 1993. Initial studies reported the detection of germline mutations in the VHL gene in 39-75% of VHL families. We used tests that detect different types of mutations to improve the frequency of detection of germline mutations in VHL families. The methods included quantitative Southern blotting to detect deletions of the entire VHL gene, Southern blotting to detect gene rearrangements, fluorescence in situ hybridization (FISH) to confirm deletions, and complete sequencing of the gene. Here we report that we have detected germline mutations in the VHL gene in 100% (93/93) of VHL families tested. In addition, we describe 13 novel intragenic VHL germline mutations. With the methodology described in this article, it is now possible to identify germline mutations in virtually all families with VHL.
希佩尔-林道病（VHL）是一种遗传性肿瘤疾病，其特征是在眼睛、大脑、脊髓、内耳、肾上腺、胰腺、肾脏和附睾中发生肿瘤。VHL肿瘤抑制基因于1993年被鉴定出来。最初的研究报告称，在39%至75%的VHL家族中检测到VHL基因的种系突变。我们使用了能检测不同类型突变的检测方法，以提高VHL家族中种系突变的检测频率。这些方法包括用于检测整个VHL基因缺失的定量Southern印迹法、用于检测基因重排的Southern印迹法、用于确认缺失的荧光原位杂交（FISH）以及该基因的完整测序。在此我们报告，在接受检测的93个VHL家族中，我们在100%（93/93）的家族中检测到了VHL基因的种系突变。此外，我们还描述了13种新的VHL基因内种系突变。采用本文所述的方法，现在几乎可以在所有VHL家族中鉴定种系突变。
