Exonic Deletion in MAN1B1 and a Missense Substitution in CAPN10 Causes Truncal Obesity, Type 2 Diabetes, Delayed Motor Development and Mild Intellectual Disability
Bibliographic record
Abstract
Abstract The Mannosidase Alpha class 1B member 1 (MAN1B1) Gene encodes the endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (ERManI) protein, which is thought to be crucial for the degradation of misfolded glycoproteins. Although there were differences in clinical features across individuals, but most patients reported had truncal obesity, facial dysphormaties, and mild to moderate intellectual disability. While the CAPN10 gene encodes cysteine protease calpain-10 is an intracellular protease (calcium-dependent) expressed ubiquitously in several tissues and involved in secretions of pancreatic β-cell insulin, translocating glucose transporter 4 to the cell membrane of adipocytes and thermogenesis. Genetic variants in CAPN10 cause diabetes type II (T2DM), obesity, and mild to moderate intellectual disability. Here, we describe the affected individuals of two different Pakistani families segregating with syndromic disorders showing clinical features of truncal obesity, motor developmental delay, and mild intellectual disability in one of the families while obesity, diabetes, and mildintellectual disability in the other family. Whole exome sequencing and Sanger sequencing led to identification of 22 bp exonic deletion in MAN1B1 (c.1833_1854del; Asp613Alafs*108) and a homozygous missense substitution in CAPN10 (c.136C>G; p.Pro46Ala). Our results not only expand the mutational spectrum of MAN1B1 and CAPN10, but also provide deeper insights by documenting clinical features and genetics findings and would prove to be a valuable addition to genetic diagnostics procedures.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".