Complex genetic architecture in severe hypobetalipoproteinemia
Bibliographic record
Abstract
BACKGROUND: Abetalipoproteinemia and homozygous hypobetalipoproteinemia are classical Mendelian autosomal recessive and co-dominant conditions, respectively, which are phenotypically similar and are usually caused by bi-allelic mutations in MTTP and APOB genes, respectively. Instances of more complex patterns of genomic variants resulting in this distinct phenotype have not been reported. METHODS: A 43 year-old male had a longstanding severe deficiency of apolipoprotein (apo) B-containing lipoproteins and circulating fat soluble vitamins consistent with either abetalipoproteinemia or homozygous familial hypobetalipoproteinemia (FHBL). He also had acanthocytosis, a long term history of fat malabsorption, and mild retinopathy, but was free from coagulopathy, myopathy and neuropathy. He had taken high dose oral fat soluble vitamins since childhood. RESULTS: Targeted next generation DNA sequencing revealed several rare heterozygous missense variants in both MTTP and APOB genes known or predicted to be deleterious, in addition to a novel heterozygous missense variant in SAR1B, which encodes the gene causing chylomicron retention disease. Evaluation of first degree relatives with mild FHBL clarified the segregation of variants. CONCLUSIONS: The proband's characteristic phenotype likely resulted from an oligogenic interaction involving multiple rare variants in MTTP and APOB, and related genes, each of which individually was associated with a milder or minimal clinical and biochemical phenotype.
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".