【摘要】 目的检测3个家族性慢性良性天疱疮(HHD)家系和3个散发病例的ATP2C1基因突变情况。方法收集3个HHD家系和3个散发病例及其家庭成员的外周血标本,提取外周血白细胞DNA,采用PCR反应扩增所有外显子编码区及其侧翼序列,通过对PCR反应产物直接测序进行序列分析。结果在3个HHD家系中发现1个新的移码突变2412delT和1个重复剪切位点突变Intron3 235-2 A→G,在3个散发病例中发现1个重复移码突变2375 delTTGT。检测新突变其家庭成员表型正常个体及100个无关正常对照不存在这样的变异,证明该新变异是突变而非正常多态性。1个HHD家系和2个散发病例未检测出ATP2C1突变。结论 2个移码突变和1个剪切位点突变可能是导致相应HHD家系和散发病例发生临床病变的原因。更多还原

【Abstract】 Objective To identify pathogenic mutations of the ATP2C1 gene in three familial and three sporadic cases of HHD. Methods We collected blood samples and clinical data from three families and three sporadic cases of HHD. Genomic DNA was extracted from peripheral blood. All the coding exons and exon-intron flanking sequences of ATP2C1 were amplified by polymerase chain reaction and products were analyzed by direct sequencing. Results One novel frame-shift mutation( 2412delT) and one splicing mutation( 235-2 A→G) from two of three HHD families and one frame-shift mutation( 2375 delTTGT) from one of three sporadic cases were present. However,no mutations were found in another family and two sporadic patients. This novel mutation was not found in unaffected family members and 100 unrelated control individuals. Conclusion Two frame-shift mutations and one splicing mutation are the underlying cause of two familial and one sporadic cases with HHD.更多还原