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目的研究一个中国人Wolfram综合征患者家系中的WFS1基因突变情况。方法应用PCR-DNA直接测序对一个Wolfram综合征患者及家系成员的WFS1基因8个外显子及其侧翼内含子进行突变筛查;采用生物信息学方法对突变蛋白的结构与功能进行估测。结果发现外显子8第417位密码子发生缺失突变,即F417del。先证者为突变纯合子,其父母为姑表亲近亲结婚,均为突变杂合子。F417del突变位于跨膜区,失去了一个非极性氨基酸。生物信息学分析提示该突变可引起跨膜区二级结构改变并使突变蛋白疏水性下降。结论本研究发现的F417del突变是一个尚未报道过的Wolfram综合征新突变。
Objective To investigate the mutation of WFS1 gene in the pedigree of a Chinese patient with Wolfram syndrome. Methods Eight exons of WFS1 gene and their flanking intron were screened by PCR-DNA direct sequencing in patients with Wolfram’s syndrome and their family members. The structure and function of muteins were estimated by bioinformatics . The result showed that codon 417 in exon 8 had a deletion mutation, namely F417del. The proband is a homozygous mutant whose parents are married to relatives of ku cousins and all are mutant heterozygotes. The F417del mutation is located in the transmembrane region and lost a non-polar amino acid. Bioinformatics analysis suggested that the mutation could cause the secondary structure of the transmembrane region to change and decrease the hydrophobicity of the mutant protein. Conclusion The F417del mutation found in this study is a new mutation of Wolfram syndrome that has not been reported yet.