【摘要】 目的:检测2个板层状鱼鳞病家系TGM1基因的突变情况。方法:采用PCR-DNA直接测序方法明确两个家系TGM1基因突变位点,并以免疫组化的方法检测其中一家系患者皮肤中转谷氨酰胺酶的活性。结果:在1个家系的患者中发现TGM1基因第13号外显子第2060位碱基发生G→A纯合突变,使密码子CGT→CAT,导致R687H突变;在另一个家系的患者中发现TGM1基因第4号内含子第一个核苷酸发生G→T及第5号外显子第760位碱基发生G→A杂合突变,分别导致IVS4+1G>T及D254N的复合杂合突变,其父母均为相应突变的携带者。在50名无关正常人中未发现相同突变。R687H纯合突变患者皮肤转谷氨酰胺酶的活性降低。结论:R687H纯合突变及D254N和IVS4+1G>T复合杂合突变为新发现的TGM1基因突变位点,可能是引起两家系板层状鱼鳞病患者的病因。更多还原

【Abstract】 Objective:To detect transglutaminase 1(TGM1) gene mutation in two Chinese families with lamellar ichthyosis.Methods:Fourteen coding exons of the TGM1 gene were amplified by PCR and DNA sequencing.The activity of epidermal transglutaminase(TGase) was determined in one of the patients,with in situ immunohistochemistry assay.Results:Three novel mutations of keratinocyte transglutaminase 1(R687H,D254N and IVS4+1G>T) were found in the two families.A homozygous R687H(CGT→CAT) mutation at exon 13 was found in one family,which resulted in 2060 G→A mutation.In another family,the D254N mutation at intron 4 caused 1 G→T mutation and the IVS4+1G>T mutation at exon 5 caused 760 G→A mutation were found.Same mutations were not found in fifty normal controls.Epidermal transglutaminase activity was decreased in the patient with R687H mutation of TGM1 gene,whose parents were carriers of the same mutation.Conclusion:Homozygous mutation of R687H and compound heterozygous mutations of D254N and IVS4 +1G>T of TGM1 gene may be the cause of lamellar ichthyosis in these two families.更多还原