Analysis of FBN1 gene variants in 15 patients with suspected Marfan syndrome and the auxiliary diagnostic value of WES
10.3760/cma.j.cn311282-20250303-00112
- VernacularTitle:15例疑似马方综合征患者的FBN1基因变异分析及WES辅助诊断价值
- Author:
Jiashan LI
1
;
Tengying GAO
;
Fang WANG
;
Yingchao ZHOU
;
Siying LIANG
;
Yan MIAO
;
Shuo LI
Author Information
1. 青岛大学附属妇女儿童医院基因检测中心，青岛 266034
- Publication Type:Journal Article
- Keywords:
FBN1 gene;
Whole exome sequencing;
Marfan syndrome;
Lipodystrophy
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(7):552-560
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.
