Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome.
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.
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Cheng
CC
Hung
Shin-Yu
SY
Lin
Chien-Nan
CN
Lee
Hui-Yu
HY
Cheng
Shuan-Pei
SP
Lin
Ming-Ren
MR
Chen
Chih-Ping
CP
Chen
Chien-Hui
CH
Chang
Chiou-Ya
CY
Lin
Chih-Chieh
CC
Yu
Hsin-Hui
HH
Chiu
Wen-Fang
WF
Cheng
Hong-Nerng
HN
Ho
Dau-Ming
DM
Niu
Yi-Ning
YN
Su
D005192:Family Health; D000071838:Fibrillin-1; D000071837:Fibrillins; D020022:Genetic Predisposition to Disease; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D013624:Taiwan; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines