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Abnormal Gs function in mitral valve prolapse dysautonomia is not associated with abnormal alpha S cDNA sequence
A Balasubramanyam1, A O Davies, J Codina
1Department of Internal Medicine, Baylor College of Medicine, Houston, Texas 77030.
Life Sciences
|January 1, 1991
Summary
Researchers found no genetic mutations in the alpha s gene of patients with mitral valve prolapse (MVP) and hyperadrenergic symptoms. This suggests other molecular defects cause abnormal G protein signaling in these patients.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- A subset of mitral valve prolapse (MVP) patients with hyperadrenergic symptoms exhibit abnormal signal transduction via the stimulatory guanine nucleotide regulatory protein (Gs).
- This abnormality involves enhanced beta-adrenergic receptor high-affinity state formation (supercoupling) and increased adenylyl cyclase activity, linked to Gs protein dysfunction.
Purpose of the Study:
- To investigate whether alterations in the nucleotide coding sequence of the alpha s gene, a key component of Gs, underlie the defective signal transduction in dysautonomic MVP patients.
- To identify the molecular basis for abnormal Gs-associated signal transduction in symptomatic MVP patients.
Main Methods:
- Cloning and sequencing of the alpha s cDNA from neutrophils of four symptomatic MVP patients and one control.
- Analysis of splice variant concentrations in the fully expressed protein.
Main Results:
- No differences were observed in the alpha s cDNA sequence between symptomatic MVP patients and the control.
- Splice variant concentrations in the fully expressed protein were also found to be unchanged in patients compared to controls.
Conclusions:
- A primary alteration in the alpha s gene coding sequence does not cause the defective Gs-associated signal transduction observed in dysautonomic MVP patients.
- The molecular lesion likely involves posttranslational modification of alpha s, defects in Gs beta/gamma subunits, or aberrant subunit interactions within the Gs protein complex.