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TP63 mutation and clefting modifier genes in an EEC syndrome family

2004· article· en· W2161135340 on OpenAlexaff
Ray Ak, ML Marazita, R Pathak, CL Beever, M.E. Cooper, Toby Goldstein, D.T. Shaw, LL Field

Bibliographic record

VenueClinical Genetics · 2004
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsUniversity of CalgaryUniversity of British ColumbiaUniversity of Toronto
FundersNational Institute of Dental and Craniofacial Research
KeywordsGeneticsMutationGeneBiologyMedicine

Abstract

fetched live from OpenAlex

Autosomal dominant EEC syndrome consists of ectrodactyly, ectodermal dysplasia, and cleft lip with or without cleft palate (CL/P). We investigated an EEC kindred with 10 affected persons in three generations in order to map the causative mutation in this family and to map modifier genes that contribute to the expression of facial clefting in the phenotype. DNA from 15 family members was genotyped for 388 genome screen markers. Analysis revealed maximal linkage between EEC and chromosome 3q27, which contains a known EEC gene - tumor protein 63 (TP63). Sequencing showed a CGT-->TGT missense mutation (R280C) in exon 7, previously reported to cause EEC in four families, and ectrodactyly alone (split hand-foot malformation) in one sporadic case and one large kindred. Analysis of the clefting phenotype in this EEC family demonstrated maximal linkage to two regions on chromosomes 4q and 14, which multiple studies have implicated in non-syndromic CL/P. In conclusion, this study demonstrates that the mutation of TP63 is the major (Mendelian) EEC gene in this kindred and suggests that additional minor modifying genes which predispose to non-syndromic CL/P could also contribute to the expression of the clefting component of the syndrome in this family.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.711
Threshold uncertainty score0.503

Codex and Gemma teacher scores by category

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

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 head0.067
GPT teacher head0.403
Teacher spread0.336 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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".

Quick stats

Citations24
Published2004
Admission routes1
Has abstractyes

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