【摘要】 目的　阐述胰岛素受体基因缺陷与胰岛素抵抗发生机制间的关系。方法　运用PCR 单链构型多态性技术 ,对 9个黑棘皮病家系 (计 9例患者 ,2 3例他们的一级亲属 )进行了该基因 17外显子筛查工作 ,对其中带型异常者进行了DNA直接测序确认。结果　发现了 3个既往未报道过的错义突变和 5个沉默多态性 (slientpolymorphism) ,即杂合子突变Val983 →Met,纯合突变Gln10 0 4 →Lys、纯合突变Gly10 2 2 →Lys、Pro980 (CCA→CCC)、Leu10 0 2 (CTG→CTT)、Gln10 0 4 (CAA→CAG)、Gly10 0 8(GGC→GGT)、Glu10 3 4(GAG→GAA)。结论　上述突变可能是造成黑棘皮病患者胰岛素抵抗的主要原因。更多还原

【Abstract】 Objective Insulin resistance clearly exists in patients with acanthosis nigricans (AN) To elucidate the mechanisms of insulin resistance in the patients with AN is very important so as to have a better understanding of non insulin dependent diabetes mellitus (NIDDM) and its related disorders Methods The techniques of PCR single strand conformation polymorphism (SSCP) and DNA direct sequencing were applied to examine the mutations and polymorphisms in the exon 17 of insulin receptor (IR) gene in 9 patients with AN and their 23 first degree relatives Results In total, 8 variant SSCP patterns were detected Direct sequencing revealed 3 point mutations, i e homozygous Val 983 → Met(GTG→ATG), homozygous Gln 1004 →Lys (CAG→AAG), heterozygous Gly 1022 →Lys(GAA→AAG) and 5 silent polymorphisms in Pro 980 (CCA CCC), Leu 1002 (CTG→CTT), Gln 1004 (CAA→CAG), Gly 1008 (GGC→GGT)and Glu 1034 (GAG→GAA) All of the three point mutations have not been mentioned in the previous literature Conclusion It is suggested that mutations in the IR gene tyrosine kinase domain causes defective kinase activity and insulin resistance更多还原