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

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

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)559-567
Number of pages9
JournalAnnals of Human Genetics
Volume73
Issue number6
DOIs
Publication statusPublished - Nov 2009
Externally publishedYes

Keywords

  • Denaturing high performance liquid chromatography (DHPLC)
  • FBN1 gene
  • Marfan syndrome
  • Multiplex ligation-dependent probe amplification (MLPA)
  • Mutation
  • Taiwan

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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