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.
Hung
Chia-Cheng
CC
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Lin
Shin-Yu
SY
Lee
Chien-Nan
CN
Cheng
Hui-Yu
HY
Lin
Shuan-Pei
SP
Chen
Ming-Ren
MR
Chen
Chih-Ping
CP
Chang
Chien-Hui
CH
Lin
Chiou-Ya
CY
Yu
Chih-Chieh
CC
Chiu
Hsin-Hui
HH
Cheng
Wen-Fang
WF
Ho
Hong-Nerng
HN
Niu
Dau-Ming
DM
Su
Yi-Ning
YN
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