Early-onset multivalvular disease caused by a missense variant in lamin A/C
Bibliographic record
Abstract
Lamins A/C, coded by LMNA gene, are crucial for nuclear architecture preservation. Pathogenic LMNA variants cause a wide range of inherited diseases called "laminopathies". A subgroup is referred to "progeroid syndromes" characterized by premature aging and other manifestations including cardiac valve abnormalities. Atypical phenotypes, generally less severe, have also been reported. We report the case of a 26-year-old male with calcific tricuspid aortic and mitral valve diseases. His father was diagnosed with severe aortic valve stenosis and mitral annulus calcification at the age of 38. The goal of this study was to identify the putative variant causing this non-syndromic multivalvular disease. Known disease-causing variants in NOTCH1, FLNA, and DCHS1 were first excluded by Sanger sequencing. Whole-exome sequencing was then performed in five family members. A LMNA variant (p.Glu262Val) was identified with in silico evidences of pathogenicity (CADD [combined annotation dependent depletion] = 33). Cells transfected with the cDNA construct harboring p.Glu262Val were characterized by abnormal nuclear morphology. Along with a literature review, the variant was classified as likely pathogenic. Elucidating the mechanism by which LMNA p.Glu262Val specifically affects cardiac heart valves is likely to provide insight about the pathogenesis of Mendelian forms of valvular heart diseases and may help guide the development of therapies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".