Related Experiment Video
Updated: Feb 4, 2026
Genome-wide Gene Deletions in Streptococcus sanguinis by High Throughput PCR
Published on: November 23, 2012
Identification of gross deletions in FBN1 gene by MLPA
Hang Yang1, Yanyun Ma1, Mingyao Luo2
1State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Background:
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene sequencing or gene-panel sequencing targeting FBN1. However, a small proportion of MFS patients carry a large genomic deletion in FBN1, which cannot be detected by routine sequencing. Here, we performed an MLPA (multiplex ligation-dependent probe amplification) test to detect large deletions and/or duplications in FBN1 and TGFBR2 in 115 unrelated Chinese patients with suspected MFS or early-onset aneurysm/dissection.
Results:
Five novel large deletions encompassing a single exon or multiple exons in the FBN1 gene were characterized in five unrelated patients, of which four were proven by Sanger sequencing, and the breakpoints were identified. Three of them met the revised Ghent criteria when genetic results were not available, and the other two patients were highly suspected and diagnosed with MFS until the FBN1 deletions were identified.
Conclusions:
Our finding expands the mutation spectrum of large FBN1 deletions and emphasizes the importance of screening for large FBN1 deletions in clinical genetic testing, especially for those with classic Marfan phenotype.
Insights
Screening for large FBN1 deletions is crucial for diagnosing Marfan syndrome (MFS). This study identified novel FBN1 deletions in Chinese patients, expanding the known mutation spectrum for this connective tissue disorder.
Area of Science:
- Genetics
- Molecular Biology
- Medical Diagnostics
Background:
- Marfan syndrome (MFS) is an inherited connective tissue disorder.
- Mutations in the FBN1 gene are the primary cause of MFS.
- Routine genetic sequencing often misses large genomic deletions in FBN1.
Purpose of the Study:
- To investigate the role of large deletions/duplications in FBN1 and TGFBR2 in Chinese patients with suspected MFS.
- To identify novel genetic variants contributing to Marfan syndrome.
Main Methods:
- Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions and duplications.
- Testing was performed on 115 unrelated Chinese patients with suspected MFS or early-onset aneurysm/dissection.
- Sanger sequencing was used to confirm identified deletions and determine breakpoints.
Main Results:
- Five novel large deletions in the FBN1 gene were identified in five unrelated patients.
- Four of these deletions were confirmed by Sanger sequencing, with breakpoints characterized.
- These deletions were critical for diagnosing MFS in patients who met clinical criteria or were highly suspected.
Conclusions:
- The study expands the known spectrum of FBN1 mutations to include large deletions.
- Highlights the importance of screening for large FBN1 deletions in clinical genetic testing for MFS.
- Emphasizes the diagnostic value of detecting FBN1 deletions in patients with classic Marfan phenotype.
Related Concept Videos
01:17Gross Anatomy of the Lungs
01:16Gross Anatomy of the Stomach
01:19Testes: Gross Anatomy
Each testis is surrounded by the tunica albuginea, a dense connective tissue layer that provides structural support and protection. This layer is covered by an outer serous membrane called the tunica vaginalis, which helps reduce friction...
01:17Gross Anatomy of Bone
The diaphysis is the tubular shaft that runs between the proximal and distal ends of the bone. The walls of the diaphysis are composed of dense and hard compact bone made of numerous osteons — the functional unit of the compact bone. The hollow region in the diaphysis is called the medullary cavity, which harbors the bone marrow. In infants and children, this marrow cavity is filled with red marrow, whereas in...
01:00Detection of Gross Error: The Q Test
01:17Gross Anatomy of the Liver
Located under the diaphragm, the liver is almost entirely ensconced within the rib cage, providing it with substantial protection. Except for the superior most bare area, the liver's surface is...