Siemens大疱性鱼鳞病1家系KRT2基因新突变

A novel missense mutation of KRT2 gene in a family with ichthyosis bullosa of Siemens

目的:检测1个Siemens大疱性鱼鳞病家系KRT2基因突变,并总结国内外相关文献。方法:提取先证者及其亲属共4人外周血DNA,对KRT2基因的全部9个外显子和侧翼序列进行PCR扩增和测序,并以150名无关系正常人作为对照。结果:先证者KRT2基因外显子第568位碱基发生G→C杂合突变(c.G568C),可导致其编码的第190位氨基酸由丙氨酸变成脯氨酸(p.A190P),该突变位点在家族患者中呈现疾病共分离现象,150名无关系正常人未检测到该突变。结论:KRT2基因的p.A190P突变可能为该家系Siemens大疱性鱼鳞病的发病原因,这个位点在国内外均属首次报道的新突变位点。

Objective： To identify a mutation of KRT2 gene in a family with ichthyosis bullosa of Siemens and review the related literatures. Methods： The DNA was extracted from the peripheral blood cells of the proband and his four relatives. All 9 exons and flanking sequences of the proband were amplified by PCR and then sequenced. PCR products of corresponding exons in KRT2 gene of other family members and 150 unrelated normal controls were directly sequenced. Results： A novel heterozygous missense mutation （c.G568C） in the 1A domain of keratin 2 was detected in the proband and his affected mother and sisters, which could lead to amino acid substitution of alanine to proline （p.Ala190Pro）. Conclusion： A novel mu- tation of KRT2 gene （p.Ala190Pro）was detected in this family with ichthyosis bullosa of Siemens,which is predictive of a missense mutation,causing the clinical phenotype.