Predominance of a rare transthyretin mutation (p.Asp38Glu) in patients with hATTR cardiomyopathy: initial data from the Croatian Transthyretin Cardiac Amyloidosis Registry (CroATTR)
Bibliographic record
Abstract
Abstract Introduction Transthyretin amyloidosis (ATTR) is classified as hereditary (hATTR) or acquired (wtATTR). hATTR is rare genetic disease with variable penetrance and phenotype, with cardiomyopathy (CM) and/or neuropathy being most relevant clinical presentations. The most common and investigated mutation in Europe is Val30Met, predominant in endemic areas of Portugal and Sweden. On the contrary, p.Asp38Glu is an extremely rare mutation with only several cases mentioned in a Swedish register and isolated cases in Japan, India and Canada. Described cases were associated with early onset CM which required specific treatment, heart- or combined heart and liver transplantation. The Croatian Transthyretin Cardiac Amyloidosis Registry (CroATTR) is a national, longitudinal, non-interventional, and both retrospective and prospective ATTR registry. It is designed to include patients with clinically proven hATTR-CM or wtATTR-CM according to the current guidelines, as well as family members with a confirmed TTR mutation. Purpose This is the first report from the CroATTR, aimed to analyse baseline characteristics of the currently enrolled patients in the first year of the registry. Methods All patient data were collected and managed using the REDCap electronic data capture tool. The collected data included demographic, clinical, diagnostic, laboratory and genetic parameters. The CroATTR registry was approved by the Institutional Ethics Committee, and all patients signed informed consent. 18 adult patients are included in this report, divided into the following groups: wtATTR group, hATTR group (genotype +, phenotype +), hATTR group (genotype +, phenotype -). Results The patients in the CroATTR Registry were predominantly male (15/18, 83%) with median age of 51 years [45.5-67] (Table 1.). Five (27.78%) patients have wATTR, seven (38.89%) have hATTR with developed CM (phenotype positive) and six (33.33%) have confirmed mutation of the TTR gene but are phenotype negative. 12 out of 13 confirmed mutations were p.Asp38Glu. Patients with hATTR CM were all male, in NYHA class I-III, with a high proportion of atrial fibrillation and amyloid-associated changes in the electrocardiogram as well as higher values of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP). Conclusion The CroATTR Registry is formed to provide insights into the prevalence, phenotypic characteristics and natural course of ATTR in Croatia. In the initial Registry analysis, to the best of our knowledge, we reported the largest number of patients with p.Asp38Glu mutation of transthyretin gene up to date. Notably, all patients with p.Asp38Glu originate from the same geographical region in the south-eastern part of Croatia, which we postulate may be a new endemic area for hATTR.Table 1
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".