国人黑斑息肉病LKB1基因胚系突变的检测

目的　研究国人家族性黑斑息肉病患者LKB1基因胚系突变情况。　方法　对确诊的4个黑斑息肉病家系取血 ,提取基因组DNA ,用PCR方法扩增每个家系中 2例患者和 1名正常成人的LKB1的 9个外显子 ,以单链构象多态性方法检测 ,对可疑突变者测序。无异常的家系再对全部编码序列测序。　结果　 4个家系中 2个家系有第 84 2位胞苷酸 (C)缺失 ,引起LKB1基因移码突变 ,产生截短蛋白。另 2个家系未见LKB1外显子序列异常。　结论　LKB1基因胚系突变是本病重要的分子遗传学基础 ,第 84 2位C缺失可能是具有中华民族特点的突变热点和始祖突变。

Germline LKB1 gene mutation screening in 4 Chinese Peutz-Jeghers syndrome pedigrees

Objective To evaluate the frequency and nature of LKB1 gene germline mutations in 4 large Chinese Peutz Jeghers syndrome pedigrees. Methods Four Chinese Peutz Jeghers syndrome pedigrees were investigated. Two patients and 1 normal adult from each pedigree were selected, and genomic DNA from peripheral blood was extracted. The 9 exons of LKB1 gene were amplified by PCR. The products were tested by SSCP and abnormally shifted bands were sequenced.If there was no positive finding in any pedigree, the entire exons were sequenced. Results The same 842 C deletion of LKB1 gene frame shift mutations was found in 2 pedigrees, which resulted in truncated protein. No exon variant was found in the left 2 pedigrees. Conclusions LKB1 gene germline mutation is an important molecular pathogen of Peutz Jeghers syndrome. 842 C deletion is a possible mutation hotspot and might be a common ancestor mutation characteristic of Chinese.