Li Dandan, Qiao Jun, Huang Dandan, Guo Ruru, Ji Jian, Liu Wei
Department of Ophthalmology, Tianjin TEDA Hospital, Tianjin, China.
Department of Ophthalmology, Lanzhou Huaxia Eye Hospital, Lanzhou, Gansu, China.
Front Med (Lausanne). 2022 Dec 13;9:1086844. doi: 10.3389/fmed.2022.1086844. eCollection 2022.
To explore the genetic defects of two families with autosomal dominant Marfan syndrome (MFS).
Two families with MFS were enrolled in this study. The detailed ocular presentations of the patients were recorded. Whole exome sequencing was performed to explore the pathogenic variants and Sanger sequencing was performed to confirm the gene mutations. Segregation analysis among the family members was made and bioinformatics analysis was performed to predict the functional impact of the mutations.
The main ocular presentations of the probands were increased axial length and ectopia lentis. Using whole exome sequencing and Sanger sequencing, a novel heterozygous missense mutation (c.5060G > C, p.Cys1687Ser) and a recurrent missense mutation (c.2168A > T, p.Asp723Val) were identified within , which were co-segregated with the MFS phenotype in the families. Evolutionary conservation analysis showed that codons 723 and 1,687 were highly conserved among several species. Functional impact predictions made using several online programs suggested that the mutations were pathogenic.
We identified a novel and a recurrent missense mutation in in two Chinese families with MFS using whole exome sequencing, and our bioinformatics analysis indicated that the mutations were disease-causing. Our results expand the mutation spectrum of and could help us better understand the genetic defects of the patients with MFS.
探索两个常染色体显性遗传马凡综合征（MFS）家系的基因缺陷。
本研究纳入两个MFS家系。记录患者详细的眼部表现。进行全外显子组测序以探索致病变异，并进行桑格测序以确认基因突变。对家庭成员进行分离分析，并进行生物信息学分析以预测突变的功能影响。
先证者的主要眼部表现为眼轴长度增加和晶状体异位。通过全外显子组测序和桑格测序，在 内鉴定出一个新的杂合错义突变（c.5060G > C，p.Cys1687Ser）和一个复发性错义突变（c.2168A > T，p.Asp723Val），这些突变在家族中与MFS表型共分离。进化保守性分析表明，密码子723和1687在几个物种中高度保守。使用多个在线程序进行的功能影响预测表明这些突变是致病的。
我们通过全外显子组测序在两个中国MFS家系的 中鉴定出一个新的和一个复发性错义突变，我们的生物信息学分析表明这些突变是致病的。我们的结果扩展了 的突变谱，并有助于我们更好地理解MFS患者的基因缺陷。
