Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome

Ma, Mingjia; Li, Zongzhe; Wang, Dao Wen; Wei, Xu

doi:10.3892/mmr.2016.5229

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Glaucoma is an assemblage of eye diseases caused due to advanced and permanent disintegration of the ganglion cells in the retina which axonal projections establish the optic nerve [ 74 ]. At present, it is considered the foremost source of irreversible blindness globally [ 71 ] that could affect >76 million people by the year 2020.…”

Section: Crispr/cas9 Is a Promising Strategy To Restore The Blindnessmentioning

confidence: 99%

CRISPR/Cas9—A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects

Ahmad

2022

IJMS

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CRISPR-based targeted genome editing is bringing revolutionary changes in the research arena of biological sciences. CRISPR/Cas9 has been explored as an efficient therapeutic tool for the treatment of genetic diseases. It has been widely used in ophthalmology research by using mouse models to correct pathogenic mutations in the eye stem cells. In recent studies, CRISPR/Cas9 has been used to correct a large number of mutations related to inherited retinal disorders. In vivo therapeutic advantages for retinal diseases have been successfully achieved in some rodents. Current advances in the CRISPR-based gene-editing domain, such as modified Cas variants and delivery approaches have optimized its application to treat blindness. In this review, recent progress and challenges of the CRISPR-Cas system have been discussed to cure blindness and its prospects.

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Section: Crispr/cas9 Is a Promising Strategy To Restore The Blindnessmentioning

confidence: 99%

CRISPR/Cas9—A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects

Ahmad

2022

IJMS

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“…4 In addition to traditional risk factors, such as hypertension and smoking, that are closely associated with aortic disease, genetic disorder–induced aortic wall weakness may cause aortic dissection. 5,6…”

Section: Introductionmentioning

confidence: 99%

“…4 In addition to traditional risk factors, such as hypertension and smoking, that are closely associated with aortic disease, genetic disorder-induced aortic wall weakness may cause aortic dissection. 5,6 The extracellular matrix (ECM), as provides elasticity and tensile strength to blood vessel walls, is the critical structural component of the aorta. Several studies have also shown that genetic factors lead to reduced elasticity and media degeneration of the aortic wall, which disrupt the homeostasis of ECM mechanical stress.…”

Section: Introductionmentioning

confidence: 99%

Fibrillin-1 Gene Polymorphisms (rs145233125, rs11070646, rs201170905) Are Associated With the Susceptibility and Clinical Prognosis of DeBakey Type III Aortic Dissection in Chinese Han Population

Sun

Chang

Jiang

et al. 2022

Journal of Cardiovascular Pharmacology

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We aim to investigate whether genetic variants of the Fibrillin-1 (FBN1) gene were associated with DeBakey type III aortic dissection (AD) and its clinical prognosis in Chinese Han population. Three single-nucleotide polymorphisms (SNPs) (rs145233125, rs11070646, rs201170905) in FBN1 were analyzed in patients with DeBakey type III AD (159) and healthy subjects (216). Geneenvironment interactions were evaluated to use generalized multifactor dimensionality reduction. Haplotype analysis of the 3 SNPs in the FBN1 gene was performed by Haploview software. Patients were followed up for average 4 years. G carriers of rs11070646 and rs201170905 in FBN1 have an increased risk of DeBakey type III AD. The interaction of FBN1 and environmental factors facilitated to the increased risk of DeBakey type III AD (cross-validation consistency = 10/10, P = 0.001). One of the most common haplotypes revealed an increased risk of DeBakey type III AD (CGG, P = 0.009). Recessive models of rs145233125 CC genotype (P , 0.05) and rs201170905 GG genotype (P , 0.001) were associated with an increased risk of death and recurrent chest pain of DeBakey type III AD. In conclusions, FBN1 gene polymorphisms contribute to DeBakey type III AD susceptibility. The interactions of gene and environment are related with the risk of DeBakey type III AD. C carriers of rs145233125 and G carriers of rs201170905 may be the adverse prognostic indicators of death and recurrent chest pain in DeBakey type III AD.

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“…14) Fibrillin-1 is a large, extracellular matrix glycoprotein that not only serves as an important calciumbinding microfibrillar structural molecule, but also serves as a regulator of TGF-β signaling. 15) In the extracellular matrix, fibrillin acts as a reservoir for transforming growth factor-β (TGF-β). Decreased deposition of fibrillin in the extracellular matrix leads to enhanced TGF-β signaling and the resultant Marfan phenotype.…”

mentioning

confidence: 99%

Three Novel Mutations in <i>FBN1</i> and <i>TGFBR2</i> in Patients with the Syndromic Form of Thoracic Aortic Aneurysms and Dissections

Cao

et al. 2018

Int. Heart J.

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There are many inherited disorders associated with thoracic aortic aneurysms and dissections (TAADs), like Marfan syndrome and Loeys-Dietz syndrome (LDS). The 4 patients in this study all had TAADs and were initially diagnosed with suspected Marfan syndrome. We collected peripheral blood samples from the patients and their family members and then attempted to identify the causal mutation using different methods including PCR, Sanger sequencing, and next generation sequencing. We identified 3 novel heterozygous mutations including 2 splicing mutations of FBN1 and 1 missense mutation of TGFBR2 in our patients. Although these mutation sites have been reported in the Human Gene Mutation Database, the nucleotide changes are different. All novel mutations found in this study were confirmed to be absent in 50 unrelated normal individuals of the same ethnic background. The RT-PCR results of 2 splicing mutations verified that the mutations can lead to the skipping of exons. The RT-qPCR results indicated that FBN1 mRNA levels were nearly 50 percent lower in the patients than in normal controls, indicating that there is almost no expression of truncated fibrillin-1 because of the nonsense-mediated mRNA decay (NMD) mechanism. To the best of our knowledge, we are the first to report these 3 novel mutations. However, the pathogenicity of these mutations still needs further confirmation. Our study has confirmed or corrected the clinical diagnosis, and enlarged the mutation spectrum of FBN1 and TGFBR2. The results should be helpful for prenatal diagnosis and genetic counseling.

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Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome

Cited by 6 publications

References 15 publications

CRISPR/Cas9—A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects

CRISPR/Cas9—A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects

Fibrillin-1 Gene Polymorphisms (rs145233125, rs11070646, rs201170905) Are Associated With the Susceptibility and Clinical Prognosis of DeBakey Type III Aortic Dissection in Chinese Han Population

Three Novel Mutations in <i>FBN1</i> and <i>TGFBR2</i> in Patients with the Syndromic Form of Thoracic Aortic Aneurysms and Dissections

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