Netherton综合征一例SPINK5基因突变研究

目的 检测Netherton综合征患者SPINK5基因的突变情况。 方法 收集患者临床资料，提取患者及其相关亲属外周血DNA，用PCR扩增SPINK5基因编码区的全部外显子及其侧翼序列并测序。 结果 直接测序发现患者SPINK5基因的第13号外显子中的第1111位碱基发生C→T杂合突变（c.1111C > T），导致其编码第371位氨基酸变为终止密码子（p.R371X）；第32号外显子中的第3121位碱基发生C→T杂合突变（c.3121C > T），导致其编码第1041位氨基酸发生错义突变（p.R1041C），其健康父母为相应突变的杂合携带者，200例健康对照未见该突变。 结论 SPINK5基因的p.R371X及p.R1041C复合杂合突变可能是引起该患者临床表现的病因之一。

Mutation analysis of the SPINK5 gene in a patient with Netherton syndrome

Xu Guiwen*, Yin Jinghua, Wang Huijun, Zhou Yun, Zhang Jie, Chen Guanzhi, Lin Zhimiao, Yang Yong, Tang Zhanli. *Department of Dermatology, Peking University First Hospital, Beijing 100034, China Corresponding author: Tang Zhanli, Email: tzldyx2012@163.com 【Abstract】 Objective To detect mutations in the SPINK5 gene in a patient with Netherton syndrome. Methods Clinical data were collected from a male patient with Netherton syndrome. Peripheral blood samples were obtained from the patient, his relatives and 200 healthy human controls. DNA was extracted from these samples, and PCR was performed to amplify all the exons and their flanking sequences in the coding region of the SPINK5 gene followed by DNA sequencing. Results Direct sequencing revealed a heterozygous nonsense mutation （c.1111C > T） in exon 13 of the SPINK5 gene, which leads to the formation of a premature termination codon at amino acid position 371 （p.R371X）, as well as a heterozygous mutation （c.3121C > T） in exon 32 of the SPINK5 gene, which leads to a missense mutation at amino acid position 1041 （p.R1041C）, in the patient. His healthy parents were heterozygous carriers of the two mutations, whereas neither of the two mutations was found in the unrelated healthy controls. Conclusion The composite heterozygous mutations p.R371X and p.R1041C in the SPINK5 gene may be partially responsible for the clinical manifestation of Netherton syndrome in this patient.