Goedbloed M A, Nellist M, Verhaaf B, Reuser A J, Lindhout D, Sunde L, Verhoef S, Halley D J, van den Ouweland A M
Department of Clinical Genetics, Erasmus University and Dijkzigt Academic Hospital, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Eur J Hum Genet. 2001 Nov;9(11):823-8. doi: 10.1038/sj.ejhg.5200728.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.
结节性硬化症(TSC)是一种常染色体显性疾病,由肿瘤抑制基因TSC1和TSC2的突变引起。我们检测到两个涉及TSC2终止密码子的序列变化,并研究了这些变化对结节蛋白(TSC2基因产物)表达以及结节蛋白与TSC1基因产物错构瘤蛋白之间结合的影响。虽然结节蛋白开放阅读框延长17个氨基酸并不干扰结节蛋白与错构瘤蛋白的结合,但更长的延伸会阻止这种相互作用。我们的数据说明了功能蛋白分析如何有助于验证和表征致病突变。