Analysis of TGFBR1*6A variant in individuals evaluated for Marfan syndrome

Area of Science:

• Genetics
• Connective Tissue Diseases
• Molecular Biology

Background:

• Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are genetic disorders of connective tissue linked to TGF-β signaling.
• Genetic variability suggests the presence of modifiers, with the TGFβR1*6A allele previously proposed as a potential low-penetrance modifier for MFS.

Purpose of the Study:

• To investigate the role of the TGFβR1*6A allele as a genetic modifier in patients with suspected MFS or related connective tissue disorders.
• To determine if the TGFβR1*6A allele is associated with specific phenotypic features, including aortic dilation, ectopia lentis, and systemic manifestations.

Main Methods:

• Retrospective review of genetic and phenotypic data from 335 patients evaluated for MFS or related disorders.
• Analysis of the association between the TGFβR1*6A allele and clinical phenotypes in diagnosed MFS patients.
• Phenotypic characterization of individuals carrying the TGFβR1*6A allele without a diagnosis of MFS.

Main Results:

• The presence of the TGFβR1*6A allele was not associated with significant phenotypic differences in patients diagnosed with Marfan syndrome.
• No altered frequency of specific connective tissue features was observed in patients carrying the TGFβR1*6A allele without MFS.
• The study did not find statistically significant evidence to support the TGFβR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features in this cohort.

Conclusions:

• In this cohort, the TGFβR1*6A allele did not emerge as a significant modifier for the primary features of Marfan syndrome or other connective tissue disorders.
• The findings suggest that other genetic or environmental factors likely contribute to the phenotypic variability observed in these conditions.