背景:先天性扁豆外翻(CEL)是一种罕见但严重的疾病。我们使用下一代测序技术在24例双侧CEL患者中检测与晶状体异常相关的基因,并寻找致病基因和突变位点。
方法:本研究共纳入2019年1月至2019年11月诊断为CEL的24例患者,收集他们的临床数据,并从外周静脉血中提取全基因组脱氧核糖核酸。采用靶向基因捕获技术,获得晶状体异常相关基因的188个外显子,使用高通量方法进行测序。通过数据分析确定突变位点,并通过Sanger方法进行验证。根据以往研究的数据,分析了基因型和临床表型之间的关联.
结果:在24名患者中,23个在原纤维蛋白-1(FBN1)基因中突变,20例被诊断为马凡氏综合征。23例FBN1突变均为杂合突变,包括17个错义突变,3个剪接变体,2外显子缺失突变,1个密码子突变,和9个新的突变。共有17个突变位于钙结合表皮生长因子结构域,包括16个含有半胱氨酸错义突变的突变。此外,在1例患者中检测到间隙连接蛋白α8(GJA8)基因的杂合突变.
结论:在这项研究中,我们在24例CEL患者中鉴定出23例FBN1基因突变和1例GJA8基因突变.其中,发现9个新的FBN1突变和14个已知突变。结果扩大了FBN1基因的突变谱,提示FBN1突变可能是中国患者CEL的主要原因。
BACKGROUND: Congenital ectopia lentis (CEL) is a rare but serious disease. We use next-generation sequencing to detect genes associated with lens abnormalities in 24 patients with bilateral CEL and search for pathogenic genes and mutation sites.
METHODS: A total of 24 patients diagnosed with CEL from January 2019 to November 2019 were enrolled in this study, and their clinical data were collected and genome-wide deoxyribonucleic acid was extracted from peripheral venous blood. Targeted gene capture technology was used to obtain 188 exons of lens abnormality-related genes, which were sequenced using a high-throughput method. The mutation sites were determined through data analysis and verified by the Sanger method. According to the data from previous studies, the association between the genotype and clinical phenotype was analysed.
RESULTS: Of the 24 patients, 23 had mutations in the fibrillin-1 (FBN1) gene, and 20 were diagnosed with Marfan syndrome. The 23 cases of FBN1 mutations were all heterozygous mutations, including 17 missense mutations, 3 splicing variants, 2 exon deletion mutations, 1 codon mutation, and 9 new mutations. A total of 17 mutations were located in the calcium-binding epidermal growth factor domain, including 16 mutations that contained missense mutations of cysteine. In addition, a heterozygous mutation of the gap junction protein alpha 8 (GJA8) gene was detected in one patient.
CONCLUSIONS: In this study, we identified 23 FBN1 gene mutations and 1 GJA8 gene mutation in 24 patients with CEL. Of these, 9 new FBN1 mutations and 14 known mutations were found. The results expanded the mutation spectrum of the FBN1 gene, suggesting that FBN1 mutation may be the main cause of CEL in Chinese patients.