论文部分内容阅读
研究目的:通过对一个中国Nance-Horan综合征家系的临床表型及基因突变分析,揭示本家系的致病遗传机制。研究方法:对该Nance-Horan综合征家系的一个男性患者进行全外显子组测序,结合此家系临床表型及遗传方式分析,选定X染色体上NHS基因上的一个无义突变c.322G>T(E108X)为可疑致病突变。通过聚合酶链式反应(PCR)和Sanger测序,对该家系内其他成员进行NHS基因突变分析,同时对50名健康对照者的NHS基因的突变检测结果进行对比。另外,将该突变的位点第108位氨基酸残基进行多物种NHS蛋白内序列比对。最后,对该家系成员眼部及全身的临床特点进行全面检查和分析。重要结论:全外显子组测序结合Sanger测序发现NHS基因第一个外显子上的c.322G>T(E108X)突变为引起该家系临床病变的突变位点;多物种NHS蛋白内序列比对发现该突变位点第108位氨基酸残基位于高度保守区;临床表型分析发现该家系内存在表型异质性。此家系为国内首次报道的无义突变引起的Nance-Horan综合征家系。
The purpose of this study was to reveal the causative genetic mechanism of this family based on the clinical phenotype and gene mutation analysis of a Chinese Nance-Horan syndrome pedigree. Methods: A male patient from the Nance-Horan syndrome pedigree was sequenced by whole exome. Based on the clinical phenotypes and genetic patterns of this pedigree, a nonsense mutation in the NHS gene on chromosome X c.322G > T (E108X) is a suspected disease-causing mutation. NHS gene mutation analysis was performed on other members of the pedigree by polymerase chain reaction (PCR) and Sanger sequencing, and the mutation detection results of NHS genes in 50 healthy controls were compared. In addition, amino acid residues at the 108th site of the mutation were subjected to sequence alignment within a multi-species NHS protein. Finally, the family members of the ocular and systemic clinical features a comprehensive examination and analysis. Important conclusion: In the whole exome sequencing combined with Sanger sequencing, the c.322G> T (E108X) mutation on the first exon of NHS gene was found to be the mutation causing the clinical pathological changes in this pedigree. It was found that the 108th amino acid residue in this mutation locus was located in a highly conserved region. Phenotypic heterogeneity was found in the pedigree by clinical phenotypic analysis. This family is the first report of a nonsense mutation caused by the Nance-Horan syndrome pedigree.