Evaluating Japanese Patients With the Marfan Syndrome Using High-Throughput Microarray-Based Mutational Analysis of Fibrillin-1 Gene

Ogawa, Naomi; Imai, Yasushi; Takahashi, Yūji; Nawata, Kan; Hara, Kazuo; Nishimura, Hiroshi; Kato, Masayoshi; Takeda, Norifumi; Kohro, Takahide; Morita, Hiroyuki; Taketani, Tsuyoshi; Morota, Tetsuro; Yamazaki, Tsutomu; Goto, Jun; Tsuji, Shoji; Takamoto, Shinichi; Nagai, Ryozo; Hirata, Yasunobu

doi:10.1016/j.amjcard.2011.07.053

Cited by 19 publications

(13 citation statements)

References 21 publications

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“…In such a setting, we developed a microarray-based high-throughput resequencing system for the efficient and accurate diagnosis of MFS. 22 In an analysis of 53 probands, 35 kinds of possible FBN1 mutations were found in 36 probands, including 23 new mutations, which were all verified on direct sequencing with 100% accuracy. There were 18 missense, nine nonsense and eight possible splicing mutations.…”

Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

“…In the revised Ghent nosology, FBN1 genetic testing has greater weight in the diagnostic assessment, although it is not mandatory. In such a setting, we developed a microarray‐based high‐throughput resequencing system for the efficient and accurate diagnosis of MFS . In an analysis of 53 probands, 35 kinds of possible FBN1 mutations were found in 36 probands, including 23 new mutations, which were all verified on direct sequencing with 100% accuracy.…”

Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

“…Genetic test, however, is not necessarily required, and it does not have 100% sensitivity and 100% specificity. Among Marfan patients who have a firm clinical diagnosis, it is possible to detect FBN1 mutations in between 60% and 90% . Even if available, caution is needed in handling genetic information, because it might cause a social disadvantage to the examinees and their relatives.…”

Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

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Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Fujita

Takeda

Imai

et al. 2014

Pediatrics International

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Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and timeconsuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.

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Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

Section: Fbn1 Mutations and Related Ethics Issuesmentioning

confidence: 99%

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Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Fujita

Takeda

Imai

et al. 2014

Pediatrics International

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“…A mutation analysis of the FBN1 gene was performed as previously described (7). Genomic DNA and mRNA isolated from white blood cells were utilized for genetic testing of FBN2 gene mutations.…”

Section: Mutation Analyses Of the Fbn1 And Fbn2 Genesmentioning

confidence: 99%

Congenital Contractural Arachnodactyly without <i>FBN1</i> or <i>FBN2</i> Gene Mutations Complicated by Dilated Cardiomyopathy

et al. 2015

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Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by marfanoid habitus with camptodactyly. However, cardiac features have rarely been documented in adults. We herein report a sporadic case of CCA in a 20-year-old woman who developed decompensated dilated cardiomyopathy. The patient did not have any mutations in the FBN1 or FBN2 genes, which are most commonly associated with Marfan syndrome and CCA, respectively. Although whether these two diseases are caused by a mutation(s) in the same gene or two different genes remains unknown, this case provides new clinical insight into the cardiovascular management of CCA.

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“…4) Accordingly, diagnoses of MFS are made using the criteria of Ghent nosology, which was established in 1996 and requires the evaluation of family history; FBN1 mutations; and skeletal, ocular, cardiovascular, and pulmonary organ systems; skin; and dura. 5) FBN1 mutations are detectable in 60-90% of patients with firm diagnoses of MFS, 6) whereas causative genes for MFS type II (MFS2), with prominent aortic/arterial phenotypes but without ectopia lentis, had not been identified until recently.…”

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confidence: 99%

Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

et al. 2016

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SummaryMarfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management. (Int Heart J 2016; 57: 271-277)

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Evaluating Japanese Patients With the Marfan Syndrome Using High-Throughput Microarray-Based Mutational Analysis of Fibrillin-1 Gene

Cited by 19 publications

References 21 publications

Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Pathophysiology and Japanese clinical characteristics in Marfan syndrome

Congenital Contractural Arachnodactyly without <i>FBN1</i> or <i>FBN2</i> Gene Mutations Complicated by Dilated Cardiomyopathy

Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

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