Abstract
In this study, we analysed the possible influence of the c.419‐43delT BMPR2 variant in patients with Graves’ disease (GD), in a molecular basis, focusing our efforts on possible alterations in the mRNA processing and synthesis. The molecular assessment of this variant in patients with GD would shed light on the association between the BMPR2 gene and the disease. The variant was detected in 18%, 55% and 10% of patients with pulmonary arterial hypertension, GD and in general population, respectively. Patients with GD fold change showed increased BMPR2 expression when matched against the controls, with a mean of 4.21 ± 1.73 (P = 0.001); BMPR2 was overexpressed in the analysed cell cycle stages. Fold change analysis of variant carriers and non‐carriers showed slight overexpression and differences between phases, but none of them were statistically significant. BMPR2 expression was confirmed in the lymphoblastoid cell lines (LCLs) with a molecular weight of 115 kD, and no differences between variant carriers and non‐carriers were detected. To conclude, the BMPR2 variant c.419‐19delT appears in high frequency in patients with GD, and independently of its presence, BMPR2 is overexpressed in the LCLs from the GD patients tested. This increase could be paired with the described decreased expression of transforming growth factor‐β1 in thyroid tissue from patients with GD.
Highlights
The BMPR2 gene (OMIM #600799) is located in the chromosome 2 position q33, and it encodes for the bone morphogenetic protein receptor of type 2 (UNIPROT #Q13873), a constitutively active serine/ threonine kinase receptor that plays a major role in the transforming growth factor beta (TGF-b; UNIPROT #P01137) superfamily regulation [1, 2]
Whenever we start to study a new mutation, a population analysis is carried out using DNA samples from general population and patients that have given their consent for the usage and storage of their anonymized genetic material by our group in future projects
The objectives of this work were to assess the presence of the c.419-43delT variation in patients with Graves’ disease (GD) and to analyse the functionality of the mutation by minigene assay for splicing alterations and quantitative real-time polymerase chain reaction (PCR) for expression measurement
Summary
The BMPR2 gene (OMIM #600799) is located in the chromosome 2 position q33, and it encodes for the bone morphogenetic protein receptor of type 2 (UNIPROT #Q13873), a constitutively active serine/ threonine kinase receptor that plays a major role in the transforming growth factor beta (TGF-b; UNIPROT #P01137) superfamily regulation [1, 2]. Whenever we start to study a new mutation, a population analysis is carried out using DNA samples from general population and patients that have given their consent for the usage and storage of their anonymized genetic material by our group in future projects.
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