Biomaterial Database

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome. 2009

Chia-Cheng Hung, and Shin-Yu Lin, and Chien-Nan Lee, and Hui-Yu Cheng, and Shuan-Pei Lin, and Ming-Ren Chen, and Chih-Ping Chen, and Chien-Hui Chang, and Chiou-Ya Lin, and Chih-Chieh Yu, and Hsin-Hui Chiu, and Wen-Fang Cheng, and Hong-Nerng Ho, and Dau-Ming Niu, and Yi-Ning Su

Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.

The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population. In this study, we screened 294 patients from 157 families for the presence of FBN1 mutations using polymerase chain reaction/ denaturing high performance liquid chromatography (PCR/DHPLC). We identified 56 mutations in 62 of the 157 (40%) families including 49 single-base substitutions (36 missense mutations, seven nonsense mutations, and six splicing sites), one small insertion, four small deletions, one small indel (insertion and deletion), and one exonic deletion (Exon 36). When family history was taken into consideration, the mutation detection rate rose to 91% (29 of 32). We further investigated the phenotypic data and found that one third (47 of 157) of the families fit the Ghent criteria for MFS. Based on that data, the mutation rate was 98% (46/47). That finding implies that family history and the Ghent criteria play a more important role than clinical manifestations in establishing a clinical diagnosis of Marfan syndrome. Among the 56 mutations found in this study, 40 (71%) have not been registered in the Human Gene Mutation Database (HGMD) or in the Universal Mutation Database (UMD). This is the first study of the mutation spectrum of MFS in a cohort of patients in Taiwan. The database is expected to considerably improve genetic counseling for and medical care of MFS families.

UI	MeSH Term	Description	Entries
D008382	Marfan Syndrome	An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE; AORTIC ANEURYSM; and AORTIC DISSECTION. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.	Marfan Like Connective Tissue Disorder,Marfan Syndrome Type 1,Marfan Syndrome Type 2,Marfan Syndrome, Type II,Marfan Syndrome, Type I,Marfan's Syndrome,Marfans Syndrome
D008840	Microfilament Proteins	Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.	Actin Binding Protein,Actin-Binding Protein,Actin-Binding Proteins,Microfilament Protein,Actin Binding Proteins,Binding Protein, Actin,Protein, Actin Binding,Protein, Actin-Binding,Protein, Microfilament,Proteins, Actin-Binding,Proteins, Microfilament
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D005192	Family Health	The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.	Health, Family
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071837	Fibrillins	A family of extracellular matrix glycoproteins that is structurally similar to LATENT TGF-BETA BINDING PROTEINS, but contain additional TGF-beta binding domains, in addition to unique domains at their N and C-terminals. Fibrillins assemble into 10-12 nm MICROFIBRILS that function in a variety of cell interactions with the EXTRACELLULAR MATRIX and developmental processes such as ELASTIC TISSUE maintenance and assembly, and the targeting of growth factors to the extracellular matrix.	Fibrillin
D000071838	Fibrillin-1	A fibrillin (FBN1) that functions as a structural support protein for MICROFIBRILS. It also regulates the maturation of OSTEOBLASTS by controlling the availability and concentration of TGF-BETA and BONE MORPHOGENETIC PROTEINS. Mutations in the FBN1 gene are associated with MARFAN SYNDROME.	Profibrillin 1,Profibrillin-1,Fibrillin 1
D013624	Taiwan	Country in eastern Asia, islands bordering the East China Sea, Philippine Sea, South China Sea, and Taiwan Strait, north of the Philippines, off the southeastern coast of China. The capital is Taipei. The alternate country name is Republic of China.	Formosa,Republic of China
D020022	Genetic Predisposition to Disease	A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.	Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic