Eggermann K, Wollmann H A, Tomiuk J, Ranke M B, Kaiser P, Eggermann T
Division of Clinical Genetics, Institute of Anthropology and Human Genetics, University of Tübingen, Germany.
Hum Hered. 1999 Jun;49(3):123-8. doi: 10.1159/000022858.
In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. Overlapping polymerase chain reaction fragments covered the whole coding sequences as well as the 5' untranslated region of the IGFBP1 and IGFBP3 genes. We detected 3 new polymorphisms in the transcribed sequence of IGFBP1, one amino acid polymorphism in exon 1 of IGFBP3 and four variants in its promotor region and in intron 1. They all occurred in similar frequencies in SRS patients and in controls. Thus, paternally inherited mutations in the promoter and coding regions of IGFBP1 and IGFBP3 genes play neither a major nor a minor role in the etiology of SRS. The newly detected polymorphisms in the coding region are powerful tools for analysis of imprinting status and for detection of possible changes in the imprinting patterns of the two genes.
在本研究中，我们试图鉴定7p12 - 13区域胰岛素样生长因子结合蛋白1和3（IGFBP1、IGFBP3）基因的遗传变异，这些变异可能通过改变蛋白质功能或表达水平而导致Silver-Russell综合征的表现。通过单链构象分析对49例Silver-Russell综合征（SRS）患者和未受影响对照的基因组DNA样本进行了研究。重叠的聚合酶链反应片段覆盖了IGFBP1和IGFBP3基因的整个编码序列以及5'非翻译区。我们在IGFBP1的转录序列中检测到3个新的多态性，在IGFBP3的外显子1中检测到1个氨基酸多态性，在其启动子区域和内含子1中检测到4个变异。它们在SRS患者和对照中的出现频率相似。因此，IGFBP1和IGFBP3基因启动子和编码区域的父系遗传突变在SRS的病因中既不起主要作用也不起次要作用。编码区域新检测到的多态性是分析印记状态和检测这两个基因印记模式可能变化的有力工具。
