P797: SATB2 variants in Glass syndrome: The clinical impact of novel variants in the context of misleading diagnoses
Bibliographic record
Abstract
lower-level mosaic 10q25.2q26.3 gain (CN=2~3) and did not detect the previously reported mosaic 8q gain.Karyotype analysis from skin biopsy at age 3 months showed a normal male chromosome complement similar to the earlier results from peripheral blood.Additional testing included negative PHOX2B gene testing for congenital central hypoventilation syndrome.Lastly, Face2Gene analysis showed that ATRX disorders were the number one match to the patient's facial features.Discussion: Similar to Pallister-Killian syndrome, could the 10q and 8q mosaic gains be indicative of novel mosaic syndromes, challenging to detect in peripheral blood as the patient gets older?What cytogenetic mechanisms could explain the presence of more than one structurally abnormal supernumerary chromosome?Mosaic duplication of 8q24.1q24.3(CN=6~7) has been previously described in the literature, reported to be identified by CMA in cord blood but not by karyotyping of cord blood in two unrelated probands with cardiac defects.Conclusion: It is unclear from these results the extent to which the ATRX VUS or the mosaic/vanishing copy number gains contribute to the patient's phenotypes.Additionally, unstable chromosomal findings of this nature may be missed if exome/genome sequencing is not performed as a front-line test at the neonatal stage.Follow-up studies recommended include methylation analysis for ATRX epigenetic signature, and optical genome mapping to characterize the structure of the mosaic gains.Introduction: Supernumerary chromosomes are structurally abnormal extra chromosomes identified by cytogenetic studies in addition to the normal complement of 46 chromosomes.They are however typically difficult to characterize at a genomic level.They can be associated with tissue-limited mosaicism and as in the case of Pallister-Killian syndrome involving tetrasomy of chromosome 12p, can be lost with time in peripheral blood leading to diagnostic challenges.Case Presentation: This 13-month-old boy presented in the neonatal intensive care unit (NICU) at day of life 1, with respiratory distress, severe hypoglycemia, microcephaly, short neck, dysmorphic facies, dysplastic ears, possible optic atrophy, hypogonadism, renal hypoplasia, petechiae, thrombocytopenia, and polycythemia.Brain MRI identified white matter hypoplasia and thin corpus callosum.The family history was significant for the patient's brother also with a history of a short NICU stay after birth with hypoglycemia, and a maternal uncle with developmental delay, failure to thrive, dysmorphic features, microcephaly, poor feeding and hypospadias.Additional medical history for the maternal uncle included meconium at delivery, negative chromosomal microarray (CMA), and brain MRI that showed partial agenesis of the corpus callosum.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.002 | 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".