A Truncated Mutant – The Most Common Sucrase‐Isomaltase Deficiency in the Inuit Population: Cellular and Biochemical Characterization
Bibliographic record
Abstract
Sucrase isomaltase (SI) is the most prominent disaccharidase in the small intestine responsible for the final steps of carbohydrate digestion. Mutations in the SI gene can lead to a drastic reduction or loss of the catalytic activity required for digestion of disaccharides, and thus can be associated with maldigestion and malabsorption of carbohydrates. Carbohydrate malabsorption is one of the most common gastrointestinal problems, where 70% of the population are affected. Congenital sucrase‐isomaltase deficiency (CSID) is an autosomal recessive disorder caused by defective SI activity; and it is clinically characterized by abdominal pain, flatulence, bloating, and diarrhea. Recently, a homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), was identified in the Inuit population with an observed allele frequency of 17.2%. In this study, Cos‐1 cells were transiently transfected with cDNA encoding the Gly92Leufs*8 mutation or SI wild‐type (SI‐WT) as a control. The assessment of this new variant phenotype was investigated through enzymatic activity measurements, cellular localization and trafficking behavior. The truncation is associated with the elimination of all N‐glycosylation sites, whereas the Ser/Thr‐rich stalk region is retained pointing to a potential O‐glycosylation. In fact, treatment with benzyl 2‐acetamido‐2‐deoxy‐α‐D‐galactopyranoside, an inhibitor of O‐glycosylation in the Golgi, resulted in a substantial shift in the size of the mutant concomitant with transport competence of the mutant to O‐glycosylation in the Golgi Apparatus. The mutant is further trafficked to the cell surface as assessed by the detection of biotinylated forms of the mutant at the cell surface. This result was also corroborated by immunofluorescence images, which revealed the mutant at the cell surface. However, this mutant does not exhibit SI activity due to the absence of the sucrase and isomaltase domains. While our data unraveled the molecular basis for the onset of the clinical symptoms in patients homozygous to this mutation, further work is needed to determine whether heterozygotes with this mutation are also affected and to which extent.
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 | 0.001 | 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 | 0.001 | 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".