一毛囊角化病家系中ATP2A2基因的突变

Mutation in ATP2A2 gene in a pedigree with keratosis follicularis

目的 :检测国内一毛囊角化病家系中ATP2A2基因的突变 ,探讨该病的发病机制。方法 :采用电镜、PCR、单链构象多态性 (singlestrandedconformationpolymorphism ,SSCP)分析和DNA测序方法。 结果 :电镜显示表皮基底细胞桥粒减少 ,张力微丝在核周凝聚。PCR SSCP方法提示ATP2A2基因 (编码肌浆网 /内质网钙离子 ATP酶 2 )第 5外显子可能存在异常 ,DNA测序证实了一种未见报道的新突变位点 :第 44 5位碱基由鸟嘌呤突变为腺嘌呤 ,使编码高度保守的 β链区第 149位氨基酸由门冬氨酸突变为门冬酰胺。 结论 :该毛囊角化病家系中存在ATP2A2基因突变 ,突变可能影响钙离子的转运 。

Objective: To study the pathogenesis and ATP2A2 gene mutation in a Chinese pedigree with keratosis follicularis. Methods: Electron microscopy, PCR SSCP and DNA sequencing were used. Results: Electron microscopy examination revealed the decrease of desmosomes in the basal cells and the perinuclear aggregation of tonofilaments. Abnormal PCR SSCP of the 5th exon of ATP2A2 gene(encoding sarco/endoplasmic reticulum Ca 2+ ATPase, type 2) was seen in the proband and his affected brother. A missense mutation of G445A which caused D149N substitution at the highly conserved β strand domain of ATP2A2 gene was confirmed by DNA sequencing. Conclusion: A novel missense mutation in ATP2A2 gene was found in a pedigree of keratosis follicularis. This mutation may alter the Ca 2+ transport, and as a consequence, impair cell adhesion and differentiation of epidermis.