DNA diagnostics of the Marfan syndrome: application of amplifiable polymorphic markers
T Rantamäki1, L Lönnqvist, L Karttunen
1Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Abstract:
The diagnosis of Marfan syndrome (MFS) is still based on careful clinical examination. There are, however, many factors creating problems in the firm establishment of the correct diagnosis. After the identification of the defective gene in MFS, fibrillin 1 (FBN1), several mutations in this gene have been reported. Since so far all but one of the mutations in FBN1 have been family specific, a common diagnostic DNA test for all MFS patients is not to be expected in the near future. Here, we have utilized four polymorphic markers in the diagnostics in MFS families from different populations. Two of the markers, FBN1a and a novel FBN1b, are intragenic markers of FBN1 and two others, D15S103 (G113) and CYP19, are very close to and most probably flank FBN1. The combined use of the multiallelic markers proved highly useful in MFS diagnostics providing informativeness in all analysed families.
Insights
Diagnosing Marfan syndrome (MFS) is challenging due to genetic complexities. Utilizing polymorphic markers linked to the fibrillin 1 (FBN1) gene significantly aids in MFS family diagnostics.
Area of Science:
- Genetics
- Molecular Biology
- Medical Diagnostics
Background:
- Marfan syndrome (MFS) diagnosis relies heavily on clinical assessment, often complicated by diagnostic challenges.
- The identification of fibrillin 1 (FBN1) as the defective gene in MFS has led to the reporting of numerous mutations.
- Currently, most FBN1 mutations are family-specific, limiting the development of a universal diagnostic DNA test for MFS.
Purpose of the Study:
- To evaluate the utility of polymorphic markers in diagnosing Marfan syndrome (MFS) within diverse family populations.
- To assess the effectiveness of intragenic and flanking markers associated with the FBN1 gene for MFS diagnostics.
Main Methods:
- Employed four polymorphic markers, including two intragenic FBN1 markers (FBN1a, FBN1b) and two flanking markers (D15S103, CYP19).
- Applied these markers in the diagnostic analysis of Marfan syndrome (MFS) families from various ethnic backgrounds.
- Utilized multiallelic markers to enhance diagnostic informativeness.
Main Results:
- The combined application of four polymorphic markers demonstrated high utility in Marfan syndrome (MFS) diagnostics.
- These markers provided informative results across all analyzed MFS families, regardless of population.
- The novel intragenic marker FBN1b proved valuable in diagnostic assessments.
Conclusions:
- Polymorphic markers, particularly when used in combination, offer a powerful tool for Marfan syndrome (MFS) diagnosis.
- This approach enhances diagnostic accuracy and informativeness, especially in the absence of a universal FBN1 mutation test.
- Further application of these markers can improve the genetic evaluation of MFS in clinical settings.
