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MG-131 ZNF259 is a candidate gene for alopecia-primordial dwarfism-renal syndrome (APDRS)

2015· article· en· W2412314591 on OpenAlexaff
Amanda Smith, Carol L. Clericuzio, Afsana Ahmed, Laura M. McDonell, Sarah L. Sawyer, Dennis E. Bulman, Kym M. Boycott

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsChildren's Hospital of Eastern Ontario
Fundersnot available
KeywordsMissense mutationBiologyMicrocephalyShort statureSanger sequencingGeneticsMicropenisExome sequencingDwarfismEndocrinologyInternal medicineMutationMedicineGeneHypospadias

Abstract

fetched live from OpenAlex

APDRS is characterised by congenital alopecia, dwarfism and hypoplastic kidneys. This syndrome was observed in 5 Hispanic New Mexican children from four families. All had symmetric intrauterine growth and progressively severe postnatal growth restriction. Skin colour is very pale with a porcelain-like appearance. Affected children have a prominent forehead, deep-set eyes, downturned corners of the mouth and full cheeks. One had cleft palate, two had shunted hydrocephalus and both males had genital hypoplasia. All had severe global delays and sensorineural hearing loss. Four children died within the first two years of life, from uremia and/or sepsis. The surviving patient is a 16 yo girl with renal failure, central fat distribution and type1 diabetes. Whole exome sequencing performed on the surviving patient and her unaffected parents yielded a homozygous missense mutation at a highly conserved locus of the ZNF259 gene, both parents were carriers. Sanger sequencing of unaffected parents and siblings of a deceased patient demonstrated parents and one sibling were heterozygous carriers of the mutation. The parents of a third affected were found to be heterozygous carriers of the same mutation, patient DNA was unavailable. These results suggest a founder mutation in these families. ZNF259 encodes a zinc finger protein that has been demonstrated to play an important role in transcription, DNA synthesis and cell proliferation. Down-regulation of ZNF259 results in arrest at G1 and G2 phases of cell cycle. Western blot on patient fibroblasts demonstrated a loss of ZNF259 protein and cell cycle analysis is currently underway.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.025
GPT teacher head0.278
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

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Citations0
Published2015
Admission routes1
Has abstractyes

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